Synaptophysin

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Gudrun Ahnert-hilger - One of the best experts on this subject based on the ideXlab platform.

  • The C-terminal transmembrane region of synaptobrevin binds Synaptophysin from adult synaptic vesicles.
    European journal of cell biology, 2005
    Co-Authors: Sowmya V. Yelamanchili, Stefan Sikorra, Thomas Binz, Anja Becher, Clemens Reisinger, Hans Bigalke, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin and synaptobrevin are abundant membrane proteins of neuronal small synaptic vesicles. In mature, differentiated neurons they form the Synaptophysin/synaptobrevin (Syp/Syb) complex. Synaptobrevin also interacts with the plasma membrane-associated proteins syntaxin and SNAP25, thereby forming the SNARE complex necessary for exocytotic membrane fusion. The two complexes are mutually exclusive. Synaptobrevin is a C-terminally membrane-anchored protein with one transmembrane domain. While its interaction with its SNARE partners is mediated exclusively by its N-terminal cytosolic region it has been unclear so far how binding to Synaptophysin is accomplished. Here, we show that synaptobrevin can be cleaved in its Synaptophysin-bound form by tetanus toxin and botulinum neurotoxin B, or by botulinum neurotoxin D, leaving shorter or longer C-terminal peptide chains bound to Synaptophysin, respectively. A recombinant, C-terminally His-tagged synaptobrevin fragment bound to nickel beads specifically bound Synaptophysin, syntaxin and SNAP25 from vesicular detergent extracts. After cleavage by tetanus toxin or botulinum toxin D light chain, the remaining C-terminal fragment no longer interacted with syntaxin or SNAP 25. In contrast, Synaptophysin was still able to bind to the residual C-terminal synaptobrevin cleavage product. In addition, the His-tagged C-terminal synaptobrevin peptide 68-116 was also able to bind Synaptophysin in detergent extracts from adult brain membranes. These data suggest that Synaptophysin interacts with the C-terminal transmembrane part of synaptobrevin, thereby allowing the N-terminal cytosolic chain to interact freely with the plasma membrane-associated SNARE proteins. Thus, by binding synaptobrevin, Synaptophysin may positively modulate neurotransmission.

  • The Synaptophysin/synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • The Synaptophysin/synaptobrevin interaction critically depends on the cholesterol content
    Journal of neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Stephanie Treiber-held, Thomas G. Ohm, Andreas Herrmann, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

  • Activity-dependent changes of the presynaptic Synaptophysin-synaptobrevin complex in adult rat brain.
    European journal of cell biology, 2001
    Co-Authors: Britta Hinz, Anja Becher, Diana Mitter, Katrin Schulze, Uwe Heinemann, Andreas Draguhn, Gudrun Ahnert-hilger
    Abstract:

    Summary The vesicular protein synaptobrevin contributes to two mutually exclusive complexes in mature synapses. Synaptobrevin tightly interacts with the plasma membrane proteins syntaxin and SNAP 25 forming the SNARE complex as a prerequisite for exocytotic membrane fusion. Alternatively, synaptobrevin binds to the vesicular protein Synaptophysin. It is unclear whether SNARE complex formation is diminished or facilitated when synaptobrevin is bound to Synaptophysin. Here we show that the Synaptophysin-synaptobrevin complex is increased in adult rat brain after repeated synaptic hyperactivity in the kindling model of epilepsy. Two days after the last kindling-induced stage V seizure the relative amount of Synaptophysin-synaptobrevin complex obtained by co-immunoprecipitation from cortical and hippocampal membranes was increased twofold compared to controls. By contrast the relative amounts of various synaptic proteins as well as that of the SNARE complex did not change in membrane preparations from kindled rats compared to controls. The increased amount of Synaptophysin-synaptobrevin complex in kindled rats supports the idea that this complex represents a reserve pool for synaptobrevin enabling synaptic vesicles to adjust to an increased demand for synaptic efficiency. We conclude that the Synaptophysin-synaptobrevin interaction is involved in activity-dependent plastic changes in adult rat brain.

  • The Synaptophysin-synaptobrevin complex: a hallmark of synaptic vesicle maturation.
    The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999
    Co-Authors: Anja Becher, Reinhard Jahn, Anne Drenckhahn, Ingrid Pahner, Martin Margittai, Gudrun Ahnert-hilger
    Abstract:

    Exocytosis of synaptic vesicles requires the formation of a fusion complex consisting of the synaptic vesicle protein synaptobrevin (vesicle-associated membrane protein, or VAMP) and the plasma membrane proteins syntaxin and soluble synaptosomal-associated protein of 25 kDa (or SNAP 25). In search of mechanisms that regulate the assembly of the fusion complex, it was found that synaptobrevin also binds to the vesicle protein Synaptophysin and that Synaptophysin-bound synaptobrevin cannot enter the fusion complex. Using a combination of immunoprecipitation, cross-linking, and in vitro interaction experiments, we report here that the Synaptophysin-synaptobrevin complex is upregulated during neuronal development. In embryonic rat brain, the complex is not detectable, although Synaptophysin and synaptobrevin are expressed and are localized to the same nerve terminals and to the same pool of vesicles. In contrast, the ability of synaptobrevin to participate in the fusion complex is detectable as early as embryonic day 14. The binding of synaptoporin, a closely related homolog of Synaptophysin, to synaptobrevin changes in a similar manner during development. Recombinant synaptobrevin binds to Synaptophysin derived from adult brain extracts but not to that derived from embryonic brain extracts. Furthermore, the soluble cytosol fraction of adult, but not of embryonic, synaptosomes contains a protein that induces Synaptophysin-synaptobrevin complex formation in embryonic vesicle fractions. We conclude that complex formation is regulated during development and is mediated by a posttranslational modification of Synaptophysin. Furthermore, we propose that the Synaptophysin-synaptobrevin complex is not essential for exocytosis but rather provides a reserve pool of synaptobrevin for exocytosis that can be readily recruited during periods of high synaptic activity.

Diana Mitter - One of the best experts on this subject based on the ideXlab platform.

  • the Synaptophysin synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of Neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnerthilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • The Synaptophysin/synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • the Synaptophysin synaptobrevin interaction critically depends on the cholesterol content
    Journal of Neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Thomas G. Ohm, Andreas Herrmann, Stephanie Treiberheld, Gudrun Ahnerthilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

  • The Synaptophysin/synaptobrevin interaction critically depends on the cholesterol content
    Journal of neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Stephanie Treiber-held, Thomas G. Ohm, Andreas Herrmann, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

  • Activity-dependent changes of the presynaptic Synaptophysin-synaptobrevin complex in adult rat brain.
    European journal of cell biology, 2001
    Co-Authors: Britta Hinz, Anja Becher, Diana Mitter, Katrin Schulze, Uwe Heinemann, Andreas Draguhn, Gudrun Ahnert-hilger
    Abstract:

    Summary The vesicular protein synaptobrevin contributes to two mutually exclusive complexes in mature synapses. Synaptobrevin tightly interacts with the plasma membrane proteins syntaxin and SNAP 25 forming the SNARE complex as a prerequisite for exocytotic membrane fusion. Alternatively, synaptobrevin binds to the vesicular protein Synaptophysin. It is unclear whether SNARE complex formation is diminished or facilitated when synaptobrevin is bound to Synaptophysin. Here we show that the Synaptophysin-synaptobrevin complex is increased in adult rat brain after repeated synaptic hyperactivity in the kindling model of epilepsy. Two days after the last kindling-induced stage V seizure the relative amount of Synaptophysin-synaptobrevin complex obtained by co-immunoprecipitation from cortical and hippocampal membranes was increased twofold compared to controls. By contrast the relative amounts of various synaptic proteins as well as that of the SNARE complex did not change in membrane preparations from kindled rats compared to controls. The increased amount of Synaptophysin-synaptobrevin complex in kindled rats supports the idea that this complex represents a reserve pool for synaptobrevin enabling synaptic vesicles to adjust to an increased demand for synaptic efficiency. We conclude that the Synaptophysin-synaptobrevin interaction is involved in activity-dependent plastic changes in adult rat brain.

Clemens Reisinger - One of the best experts on this subject based on the ideXlab platform.

  • The C-terminal transmembrane region of synaptobrevin binds Synaptophysin from adult synaptic vesicles.
    European journal of cell biology, 2005
    Co-Authors: Sowmya V. Yelamanchili, Stefan Sikorra, Thomas Binz, Anja Becher, Clemens Reisinger, Hans Bigalke, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin and synaptobrevin are abundant membrane proteins of neuronal small synaptic vesicles. In mature, differentiated neurons they form the Synaptophysin/synaptobrevin (Syp/Syb) complex. Synaptobrevin also interacts with the plasma membrane-associated proteins syntaxin and SNAP25, thereby forming the SNARE complex necessary for exocytotic membrane fusion. The two complexes are mutually exclusive. Synaptobrevin is a C-terminally membrane-anchored protein with one transmembrane domain. While its interaction with its SNARE partners is mediated exclusively by its N-terminal cytosolic region it has been unclear so far how binding to Synaptophysin is accomplished. Here, we show that synaptobrevin can be cleaved in its Synaptophysin-bound form by tetanus toxin and botulinum neurotoxin B, or by botulinum neurotoxin D, leaving shorter or longer C-terminal peptide chains bound to Synaptophysin, respectively. A recombinant, C-terminally His-tagged synaptobrevin fragment bound to nickel beads specifically bound Synaptophysin, syntaxin and SNAP25 from vesicular detergent extracts. After cleavage by tetanus toxin or botulinum toxin D light chain, the remaining C-terminal fragment no longer interacted with syntaxin or SNAP 25. In contrast, Synaptophysin was still able to bind to the residual C-terminal synaptobrevin cleavage product. In addition, the His-tagged C-terminal synaptobrevin peptide 68-116 was also able to bind Synaptophysin in detergent extracts from adult brain membranes. These data suggest that Synaptophysin interacts with the C-terminal transmembrane part of synaptobrevin, thereby allowing the N-terminal cytosolic chain to interact freely with the plasma membrane-associated SNARE proteins. Thus, by binding synaptobrevin, Synaptophysin may positively modulate neurotransmission.

  • the Synaptophysin synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of Neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnerthilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • The Synaptophysin/synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • The Synaptophysin/synaptobrevin interaction critically depends on the cholesterol content
    Journal of neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Stephanie Treiber-held, Thomas G. Ohm, Andreas Herrmann, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

  • the Synaptophysin synaptobrevin interaction critically depends on the cholesterol content
    Journal of Neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Thomas G. Ohm, Andreas Herrmann, Stephanie Treiberheld, Gudrun Ahnerthilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

Britta Hinz - One of the best experts on this subject based on the ideXlab platform.

  • the Synaptophysin synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of Neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnerthilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • The Synaptophysin/synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • the Synaptophysin synaptobrevin interaction critically depends on the cholesterol content
    Journal of Neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Thomas G. Ohm, Andreas Herrmann, Stephanie Treiberheld, Gudrun Ahnerthilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

  • The Synaptophysin/synaptobrevin interaction critically depends on the cholesterol content
    Journal of neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Stephanie Treiber-held, Thomas G. Ohm, Andreas Herrmann, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

  • Activity-dependent changes of the presynaptic Synaptophysin-synaptobrevin complex in adult rat brain.
    European journal of cell biology, 2001
    Co-Authors: Britta Hinz, Anja Becher, Diana Mitter, Katrin Schulze, Uwe Heinemann, Andreas Draguhn, Gudrun Ahnert-hilger
    Abstract:

    Summary The vesicular protein synaptobrevin contributes to two mutually exclusive complexes in mature synapses. Synaptobrevin tightly interacts with the plasma membrane proteins syntaxin and SNAP 25 forming the SNARE complex as a prerequisite for exocytotic membrane fusion. Alternatively, synaptobrevin binds to the vesicular protein Synaptophysin. It is unclear whether SNARE complex formation is diminished or facilitated when synaptobrevin is bound to Synaptophysin. Here we show that the Synaptophysin-synaptobrevin complex is increased in adult rat brain after repeated synaptic hyperactivity in the kindling model of epilepsy. Two days after the last kindling-induced stage V seizure the relative amount of Synaptophysin-synaptobrevin complex obtained by co-immunoprecipitation from cortical and hippocampal membranes was increased twofold compared to controls. By contrast the relative amounts of various synaptic proteins as well as that of the SNARE complex did not change in membrane preparations from kindled rats compared to controls. The increased amount of Synaptophysin-synaptobrevin complex in kindled rats supports the idea that this complex represents a reserve pool for synaptobrevin enabling synaptic vesicles to adjust to an increased demand for synaptic efficiency. We conclude that the Synaptophysin-synaptobrevin interaction is involved in activity-dependent plastic changes in adult rat brain.

Sowmya V. Yelamanchili - One of the best experts on this subject based on the ideXlab platform.

  • The C-terminal transmembrane region of synaptobrevin binds Synaptophysin from adult synaptic vesicles.
    European journal of cell biology, 2005
    Co-Authors: Sowmya V. Yelamanchili, Stefan Sikorra, Thomas Binz, Anja Becher, Clemens Reisinger, Hans Bigalke, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin and synaptobrevin are abundant membrane proteins of neuronal small synaptic vesicles. In mature, differentiated neurons they form the Synaptophysin/synaptobrevin (Syp/Syb) complex. Synaptobrevin also interacts with the plasma membrane-associated proteins syntaxin and SNAP25, thereby forming the SNARE complex necessary for exocytotic membrane fusion. The two complexes are mutually exclusive. Synaptobrevin is a C-terminally membrane-anchored protein with one transmembrane domain. While its interaction with its SNARE partners is mediated exclusively by its N-terminal cytosolic region it has been unclear so far how binding to Synaptophysin is accomplished. Here, we show that synaptobrevin can be cleaved in its Synaptophysin-bound form by tetanus toxin and botulinum neurotoxin B, or by botulinum neurotoxin D, leaving shorter or longer C-terminal peptide chains bound to Synaptophysin, respectively. A recombinant, C-terminally His-tagged synaptobrevin fragment bound to nickel beads specifically bound Synaptophysin, syntaxin and SNAP25 from vesicular detergent extracts. After cleavage by tetanus toxin or botulinum toxin D light chain, the remaining C-terminal fragment no longer interacted with syntaxin or SNAP 25. In contrast, Synaptophysin was still able to bind to the residual C-terminal synaptobrevin cleavage product. In addition, the His-tagged C-terminal synaptobrevin peptide 68-116 was also able to bind Synaptophysin in detergent extracts from adult brain membranes. These data suggest that Synaptophysin interacts with the C-terminal transmembrane part of synaptobrevin, thereby allowing the N-terminal cytosolic chain to interact freely with the plasma membrane-associated SNARE proteins. Thus, by binding synaptobrevin, Synaptophysin may positively modulate neurotransmission.

  • the Synaptophysin synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of Neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnerthilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • The Synaptophysin/synaptobrevin complex dissociates independently of neuroexocytosis
    Journal of neurochemistry, 2004
    Co-Authors: Clemens Reisinger, Anja Becher, Britta Hinz, Diana Mitter, Sowmya V. Yelamanchili, Hans Bigalke, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to Synaptophysin or when existing as a homodimer. The Synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with alpha-latrotoxin or Ca(2+)-ionophores dissociates the Synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the Synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the Synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from Synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the Synaptophysin/synaptobrevin complex may play in mature neurones.

  • The Synaptophysin/synaptobrevin interaction critically depends on the cholesterol content
    Journal of neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Stephanie Treiber-held, Thomas G. Ohm, Andreas Herrmann, Gudrun Ahnert-hilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

  • the Synaptophysin synaptobrevin interaction critically depends on the cholesterol content
    Journal of Neurochemistry, 2002
    Co-Authors: Diana Mitter, Britta Hinz, Clemens Reisinger, Susanne Hollmann, Sowmya V. Yelamanchili, Thomas G. Ohm, Andreas Herrmann, Stephanie Treiberheld, Gudrun Ahnerthilger
    Abstract:

    Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The Synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of Synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the Synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the Synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the Synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the Synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the Synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

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