The Experts below are selected from a list of 2298 Experts worldwide ranked by ideXlab platform

Pietro De Camilli - One of the best experts on this subject based on the ideXlab platform.

  • Amphiphysin II (SH3P9; BIN1), a Member of the Amphiphysin/Rvs Family, Is Concentrated in the Cortical Cytomatrix of Axon Initial Segments and Nodes of Ranvier in Brain and around T Tubules in Skeletal Muscle
    2013
    Co-Authors: Margaret Husta Butler, Detlev Grabs, Carol David, Laurie Daniell, Gian Carlo Ochoa, Zachary Freyberg, Ottavio Cremona, Pietro De Camilli
    Abstract:

    Abstract. Amphiphysin (Amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man syndrome, is a neuronal protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. The yeast homologue of Amphiphysin, Rvs167, has pleiotropic functions, including a role in endocytosis and in actin dynamics, suggesting that Amphiphysin may also be implicated in the function of the presynaptic actin cytoskeleton. We report here the characterization of a second mammalian Amphiphysin gene, Amphiphysin II (SH3P9; BIN1), which encodes products primarily expressed in skeletal muscle and brain, as differentially spliced isoforms. In skeletal muscle, Amphiphysin II is concentrated around T tubules, while in brain it is concentrated in the cytomatrix beneath the plasmamembran

  • Dynamic interaction of Amphiphysin with N-WASP regulates actin assembly.
    Journal of Biological Chemistry, 2009
    Co-Authors: Hiroshi Yamada, Pietro De Camilli, Fabio Benfenati, Ottavio Cremona, Sergi Padilla-parra, Sun-joo Park, Toshiki Itoh, Mathilde Chaineau, Ilaria Monaldi, Maïté Coppey-moisan
    Abstract:

    Amphiphysin 1, an endocytic adaptor concentrated at synapses that couples clathrin-mediated endocytosis to dynamin-dependent fission, was also shown to have a regulatory role in actin dynamics. Here, we report that Amphiphysin 1 interacts with N-WASP and stimulates N-WASP- and Arp2/3-dependent actin polymerization. Both the Src homology 3 and the N-BAR domains are required for this stimulation. Acidic liposome-triggered, N-WASP-dependent actin polymerization is strongly impaired in brain cytosol of Amphiphysin 1 knock-out mice. FRET-FLIM analysis of Sertoli cells, where endogenously expressed Amphiphysin 1 co-localizes with N-WASP in peripheral ruffles, confirmed the association between the two proteins in vivo. This association undergoes regulation and is enhanced by stimulating phosphatidylserine receptors on the cell surface with phosphatidylserine-containing liposomes that trigger ruffle formation. These results indicate that actin regulation is a key function of Amphiphysin 1 and that such function cooperates with the endocytic adaptor role and membrane shaping/curvature sensing properties of the protein during the endocytic reaction.

  • the stimulatory action of Amphiphysin on dynamin function is dependent on lipid bilayer curvature
    The EMBO Journal, 2004
    Co-Authors: Yumi Yoshida, Masahiro Kinuta, Shuang Liang, Tadashi Abe, Ottavio Cremona, Kenta Araki, Gilbert Di Paolo, Yoshinori Moriyama, Tatsuji Yasuda, Pietro De Camilli
    Abstract:

    Amphiphysin is a major dynamin-binding partner at the synapse; however, its function in fission is unclear. Incubation of large unilamellar liposomes with mice brain cytosol led to massive formation of small vesicles, whereas cytosol of Amphiphysin 1 knockout mice was much less efficient in this reaction. Vesicle formation from large liposomes by purified dynamin was also strongly enhanced by Amphiphysin. In the presence of liposomes, Amphiphysin strongly affected dynamin GTPase activity and the recruitment of dynamin to the liposomes, but this activity was highly dependent on liposome size. Deletion from Amphiphysin of its central proline-rich stretch dramatically potentiated its effect on dynamin, possibly by relieving an inhibitory intramolecular interaction. These results suggest a model in which maturation of endocytic pits correlates with the oligomerization of dynamin with either Amphiphysin or other proteins with similar domain structure. Formation of these complexes is coupled to the activation of dynamin GTPase activity, thus explaining how deep invagination of the pit leads to fission.

  • Amphiphysin is a component of clathrin coats formed during synaptic vesicle recycling at the lamprey giant synapse.
    Traffic (Copenhagen Denmark), 2004
    Co-Authors: Emma Evergren, Vladimir I. Slepnev, Melissa Marcucci, Fredrik Andersson, Peter Löw, Nikolay Tomilin, Helge Gad, Pietro De Camilli
    Abstract:

    Amphiphysin is a protein enriched at mammalian synapses thought to function as a clathrin accessory factor in synaptic vesicle endocytosis. Here we examine the involvement of Amphiphysin in synaptic vesicle recycling at the giant synapse in the lamprey. We show that Amphiphysin resides in the synaptic vesicle cluster at rest and relocates to sites of endocytosis during synaptic activity. It accumulates at coated pits where its SH3 domain, but not its central clathrin/AP-2-binding (CLAP) region, is accessible for antibody binding. Microinjection of antibodies specifically directed against the CLAP region inhibited recycling of synaptic vesicles and caused accumulation of clathrin-coated intermediates with distorted morphology, including flat patches of coated presynaptic membrane. Our data provide evidence for an activity-dependent redistribution of Amphiphysin in intact nerve terminals and show that Amphiphysin is a component of presynaptic clathrin-coated intermediates formed during synaptic vesicle recycling.

  • rhabdomyolysis and paraneoplastic stiff man syndrome with Amphiphysin autoimmunity
    Annals of Neurology, 2004
    Co-Authors: Gabor C Petzold, Melissa Marcucci, Michele Solimena, Margaret H. Butler, Frank K H Van Landeghem, Karl M Einhaupl, Jose M Valdueza, Pietro De Camilli
    Abstract:

    Stiff-Man syndrome (SMS) is a rare disease of the central nervous system characterized by chronic muscle rigidity and autoimmunity directed against synaptic antigens. In a subset of patients, generally positive for antiAmphiphysin autoantibodies, SMS has an autoimmune paraneoplastic origin. Amphiphysin isoforms are expressed at high levels in brain and skeletal muscle and often are overexpressed in breast cancer. We report here the occurrence of rhabdomyolysis in a patient with SMS, breast cancer, and antibodies that recognize both brain and muscle Amphiphysin isoforms. Immunotherapy induced a remission of both rhabdomyolysis and SMS symptoms. Autoimmune rhabdomyolysis may represent a paraneoplastic complication of cancer patients with Amphiphysin autoimmunity.

Harvey T Mcmahon - One of the best experts on this subject based on the ideXlab platform.

  • cooperative recruitment of dynamin and bin Amphiphysin rvs bar domain containing proteins leads to gtp dependent membrane scission
    Journal of Biological Chemistry, 2013
    Co-Authors: Michael Meinecke, Emmanuel Boucrot, Gamze Camdere, Waiching Hon, Rohit Mittal, Harvey T Mcmahon
    Abstract:

    Dynamin mediates various membrane fission events, including the scission of clathrin-coated vesicles. Here, we provide direct evidence for cooperative membrane recruitment of dynamin with the BIN/Amphiphysin/Rvs (BAR) proteins, endophilin and Amphiphysin. Surprisingly, endophilin and Amphiphysin recruitment to membranes was also dependent on binding to dynamin due to auto-inhibition of BAR-membrane interactions. Consistent with reciprocal recruitment in vitro, dynamin recruitment to the plasma membrane in cells was strongly reduced by concomitant depletion of endophilin and Amphiphysin, and conversely, depletion of dynamin dramatically reduced the recruitment of endophilin. In addition, Amphiphysin depletion was observed to severely inhibit clathrin-mediated endocytosis. Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins. Thus, BAR domain proteins and dynamin act in synergy in membrane recruitment and GTP-dependent vesicle scission.

  • solitary and repetitive binding motifs for the ap2 complex α appendage in Amphiphysin and other accessory proteins
    Journal of Biological Chemistry, 2008
    Co-Authors: Lene E Olesen, Yvonne Vallis, Harvey T Mcmahon, Ian G Mills, Marijn G J Ford, Eva M Schmid, Madan M Babu, Gerrit J K Praefcke
    Abstract:

    Adaptor protein (AP) complexes bind to transmembrane proteins destined for internalization and to membrane lipids, so linking cargo to the accessory internalization machinery. This machinery interacts with the appendage domains of APs, which have platform and β-sandwich subdomains, forming the binding surfaces for interacting proteins. Proteins that interact with the subdomains do so via short motifs, usually found in regions of low structural complexity of the interacting proteins. So far, up to four motifs have been identified that bind to and partially compete for at least two sites on each of the appendage domains of the AP2 complex. Motifs in individual accessory proteins, their sequential arrangement into motif domains, and partial competition for binding sites on the appendage domains coordinate the formation of endocytic complexes in a temporal and spatial manner. In this work, we examine the dominant interaction sequence in Amphiphysin, a synapse-enriched accessory protein, which generates membrane curvature and recruits the scission protein dynamin to the necks of coated pits, for the platform subdomain of the α-appendage. The motif domain of Amphiphysin1 contains one copy of each of a DX(F/W) and FXDXF motif. We find that the FXDXF motif is the main determinant for the high affinity interaction with the α-adaptin appendage. We describe the optimal sequence of the FXDXF motif using thermodynamic and structural data and show how sequence variation controls the affinities of these motifs for the α-appendage.

  • bar domains as sensors of membrane curvature the Amphiphysin bar structure
    Science, 2004
    Co-Authors: Brian J Peter, Philip R Evans, Helen M Kent, Ian G Mills, Yvonne T Vallis, Jonathan P G Butler, Harvey T Mcmahon
    Abstract:

    The BAR (Bin/Amphiphysin/Rvs) domain is the most conserved feature in Amphiphysins from yeast to human and is also found in endophilins and nadrins. We solved the structure of the Drosophila Amphiphysin BAR domain. It is a crescent-shaped dimer that binds preferentially to highly curved negatively charged membranes. With its N-terminal amphipathic helix and BAR domain (N-BAR), Amphiphysin can drive membrane curvature in vitro and in vivo. The structure is similar to that of arfaptin2, which we find also binds and tubulates membranes. From this, we predict that BAR domains are in many protein families, including sorting nexins, centaurins, and oligophrenins. The universal and minimal BAR domain is a dimerization, membrane-binding, and curvature-sensing module.

  • Amphiphysin is necessary for organization of the excitation contraction coupling machinery of muscles but not for synaptic vesicle endocytosis in drosophila
    Genes & Development, 2001
    Co-Authors: Azam Razzaq, Harvey T Mcmahon, Andrew C Zelhof, Iain M Robinson, Jeremy N Skepper, Antony P Jackson, Cahir J Okane
    Abstract:

    Amphiphysins 1 and 2 are enriched in the mammalian brain and are proposed to recruit dynamin to sites of endocytosis. Shorter Amphiphysin 2 splice variants are also found ubiquitously, with an enrichment in skeletal muscle. At the Drosophila larval neuromuscular junction, Amphiphysin is localized postsynaptically and Amphiphysin mutants have no major defects in neurotransmission; they are also viable, but flightless. Like mammalian Amphiphysin 2 in muscles, Drosophila Amphiphysin does not bind clathrin, but can tubulate lipids and is localized on T-tubules. Amphiphysin mutants have a novel phenotype, a severely disorganized T-tubule/sarcoplasmic reticulum system. We therefore propose that muscle Amphiphysin is not involved in clathrin-mediated endocytosis, but in the structural organization of the membrane-bound compartments of the excitation–contraction coupling machinery of muscles.

  • crystal structure of the Amphiphysin 2 sh3 domain and its role in the prevention of dynamin ring formation
    The EMBO Journal, 1998
    Co-Authors: David J Owen, Yvonne Vallis, Patrick Wigge, Philip R Evans, J D A Moore, Harvey T Mcmahon
    Abstract:

    The Amphiphysins are brain-enriched proteins, implicated in clathrin-mediated endocytosis, that interact with dynamin through their SH3 domains. To elucidate the nature of this interaction, we have solved the crystal structure of the Amphiphysin-2 (Amph2) SH3 domain to 2.2 A. The structure possesses several notable features, including an extensive patch of negative electrostatic potential covering a large portion of its dynamin binding site. This patch accounts for the specific requirement of Amphiphysin for two arginines in the proline-rich binding motif to which it binds on dynamin. We demonstrate that the interaction of dynamin with Amphiphysin SH3 domains, unlike that with SH3 domains of Grb2 or spectrin, prevents dynamin self-assembly into rings. Deletion of a unique insert in the n-Src loop of Amph2 SH3, a loop adjacent to the dynamin binding site, significantly reduces this effect. Conversely, replacing the n-Src loop of the N-terminal SH3 domain of Grb2 with that of Amph2 causes it to favour dynamin ring disassembly. Transferrin uptake assays show that shortening the n-Src loop of Amph2 SH3 reduces the ability of this domain to inhibit endocytosis in vivo. Our data suggest that Amphiphysin SH3 domains are important regulators of the multimerization cycle of dynamin in endocytosis.

Patrick Wigge - One of the best experts on this subject based on the ideXlab platform.

  • crystal structure of the Amphiphysin 2 sh3 domain and its role in the prevention of dynamin ring formation
    The EMBO Journal, 1998
    Co-Authors: David J Owen, Yvonne Vallis, Patrick Wigge, Philip R Evans, J D A Moore, Harvey T Mcmahon
    Abstract:

    The Amphiphysins are brain-enriched proteins, implicated in clathrin-mediated endocytosis, that interact with dynamin through their SH3 domains. To elucidate the nature of this interaction, we have solved the crystal structure of the Amphiphysin-2 (Amph2) SH3 domain to 2.2 A. The structure possesses several notable features, including an extensive patch of negative electrostatic potential covering a large portion of its dynamin binding site. This patch accounts for the specific requirement of Amphiphysin for two arginines in the proline-rich binding motif to which it binds on dynamin. We demonstrate that the interaction of dynamin with Amphiphysin SH3 domains, unlike that with SH3 domains of Grb2 or spectrin, prevents dynamin self-assembly into rings. Deletion of a unique insert in the n-Src loop of Amph2 SH3, a loop adjacent to the dynamin binding site, significantly reduces this effect. Conversely, replacing the n-Src loop of the N-terminal SH3 domain of Grb2 with that of Amph2 causes it to favour dynamin ring disassembly. Transferrin uptake assays show that shortening the n-Src loop of Amph2 SH3 reduces the ability of this domain to inhibit endocytosis in vivo. Our data suggest that Amphiphysin SH3 domains are important regulators of the multimerization cycle of dynamin in endocytosis.

  • the Amphiphysin family of proteins and their role in endocytosis at the synapse
    Trends in Neurosciences, 1998
    Co-Authors: Patrick Wigge, Harvey T Mcmahon
    Abstract:

    Clathrin-mediated endocytosis at the plasma membrane is a major pathway of synaptic vesicle recycling in neurones, but little is known about the molecular machinery that orchestrates the process. The Amphiphysin protein has recently emerged into the limelight since its discovery in 1992 as a synaptic vesicle-associated protein. It was subsequently found to interact in vitro with the GTPase dynamin through its SH3 domain. However, only in the past year has its role in endocytosis been confirmed, with the demonstration that the introduction of dominant-negative-acting SH3 domains into living cells causes a potent blockade of clathrin-mediated endocytosis. This, together with the discovery by several groups of a second nerve terminal-enriched Amphiphysin isoform, and the finding that the two proteins heterodimerize, further suggests that the Amphiphysins are closely connected with dynamin-mediated vesicle budding. This review summarizes current views in the field, and draws on data that suggest intriguing alternative roles--including possible involvement in the cytoskeleton and in tumour suppression--for certain members of the Amphiphysin family.

  • Amphiphysin Heterodimers: Potential Role in Clathrin-mediated Endocytosis
    Molecular Biology of the Cell, 1997
    Co-Authors: Patrick Wigge, Yvonne Vallis, David J Owen, Katinka Köhler, Christopher A. Doyle, Sp Hunt, Harvey T Mcmahon
    Abstract:

    Amphiphysin (Amph) is a src homology 3 domain-containing protein that has been implicated in synaptic vesicle endocytosis as a result of its interaction with dynamin. In a screen for novel members of the Amphiphysin family, we identified Amph2, an isoform 49% identical to the previously characterized Amph1 protein. The subcellular distribution of this isoform parallels Amph1, both being enriched in nerve terminals. Like Amph1, a role in endocytosis at the nerve terminal is supported by the rapid dephosphorylation of Amph2 on depolarization. Importantly, the two isoforms can be coimmunoprecipitated from the brain as an equimolar complex, suggesting that the two isoforms act in concert. As determined by cross-linking of brain extracts, the Amph1‐Amph2 complex is a 220- to 250-kDa heterodimer. COS cells transfected with either Amph1 or Amph2 show greatly reduced transferrin uptake, but coexpression of the two proteins rescues this defect, supporting a role for the heterodimer in clathrin-mediated endocytosis. Although the src homology 3 domains of both isoforms interact with dynamin, the heterodimer can associate with multiple dynamin molecules in vitro and activates dynamin’s GTPase activity. We propose that it is an Amphiphysin heterodimer that drives the recruitment of dynamin to clathrin-coated pits in endocytosing nerve terminals.

  • Clathrin interacts specifically with Amphiphysin and is displaced by dynamin
    FEBS Letters, 1997
    Co-Authors: Harvey T Mcmahon, Patrick Wigge, Corrin Smith
    Abstract:

    Amphiphysin is an SH3 domain protein that has been implicated in synaptic vesicle endocytosis. We have recently cloned a second Amphiphysin isoform, Amph2 (sequence submitted to GenBank, Y13380). Proteins capable of forming a complex with Amphiphysin were isolated from rat brain by using recombinant GST-Amph2 for binding experiments. As well as interacting with dynamin I, the full-length protein bound to a weaker 180-kDa band. Immunoblotting demonstrated this protein to be clathrin. To address whether this is a direct interaction, the clathrin binding to Amphiphysin was reconstituted in vitro with purified proteins. The N-terminal domain of Amph2 is sufficient for clathrin binding. Dynamin, which interacts with the SH3 domain of Amph2, displaces clathrin from the N-terminus. We propose a model that may explain how clathrin and dynamin are recruited to non-overlapping sites of the coated pit.

  • inhibition of receptor mediated endocytosis by the Amphiphysin sh3 domain
    Current Biology, 1997
    Co-Authors: Patrick Wigge, Yvonne Vallis, Harvey T Mcmahon
    Abstract:

    Abstract Background: Receptor-mediated endocytosis appears to require the GTP-binding protein dynamin, but the process by which dynamin is recruited to clathrin-coated pits remains unclear. Dynamin contains several proline-rich clusters that bind to Src homology 3 (SH3) domains, which are short modules found in many signalling proteins and which mediate protein–protein interactions. Amphiphysin, a protein that is highly expressed in the brain, interacts with dynamin in vitro , as do Grb2 and many other SH3 domain-containing proteins. In this study, we examined the role of Amphiphysin in receptor-mediated endocytosis in vivo . Results: To address the importance of the Amphiphysin SH3 domain in dynamin recruitment, we used a transferrin and epidermal growth factor (EGF) uptake assay in COS-7 fibroblasts. Amphiphysin is present in these cells at a low level and indeed in other peripheral tissues. Confocal immunofluorescence revealed that cells transfected with the Amphiphysin SH3 domain showed a potent blockade in receptor-mediated endocytosis. To test whether the cellular target of Amphiphysin is dynamin, COS-7 cells were cotransfected with both dynamin and the Amphiphysin SH3 domain; here, transferrin uptake was efficiently rescued. Importantly, the SH3 domains of Grb2, phospholipase C γ and spectrin all failed to exert any effect on endocytosis. The mechanism of Amphiphysin action in recruiting dynamin was additionally tested in vitro : Amphiphysin could associate with both dynamin and α -adaptin simultaneously, further supporting a role for Amphiphysin in endocytosis. Conclusions: Our results suggest that the SH3 domain of Amphiphysin recruits dynamin to coated pits in vivo , probably via plasma membrane adaptor complexes. We propose that Amphiphysin is not only required for synapticvesicle endocytosis, but might also be a key player in dynamin recruitment in all cells undergoing receptor-mediated endocytosis.

Margaret H. Butler - One of the best experts on this subject based on the ideXlab platform.

  • rhabdomyolysis and paraneoplastic stiff man syndrome with Amphiphysin autoimmunity
    Annals of Neurology, 2004
    Co-Authors: Gabor C Petzold, Melissa Marcucci, Michele Solimena, Margaret H. Butler, Frank K H Van Landeghem, Karl M Einhaupl, Jose M Valdueza, Pietro De Camilli
    Abstract:

    Stiff-Man syndrome (SMS) is a rare disease of the central nervous system characterized by chronic muscle rigidity and autoimmunity directed against synaptic antigens. In a subset of patients, generally positive for antiAmphiphysin autoantibodies, SMS has an autoimmune paraneoplastic origin. Amphiphysin isoforms are expressed at high levels in brain and skeletal muscle and often are overexpressed in breast cancer. We report here the occurrence of rhabdomyolysis in a patient with SMS, breast cancer, and antibodies that recognize both brain and muscle Amphiphysin isoforms. Immunotherapy induced a remission of both rhabdomyolysis and SMS symptoms. Autoimmune rhabdomyolysis may represent a paraneoplastic complication of cancer patients with Amphiphysin autoimmunity.

  • tandem arrangement of the clathrin and ap 2 binding domains in Amphiphysin 1 and disruption of clathrin coat function by Amphiphysin fragments comprising these sites
    Journal of Biological Chemistry, 2000
    Co-Authors: Vladimir I. Slepnev, Gian Carlo Ochoa, Margaret H. Butler, Pietro De Camilli
    Abstract:

    Amphiphysin 1 and 2 are proteins implicated in the recycling of synaptic vesicles in nerve terminals. They interact with dynamin and synaptojanin via their COOH-terminal SH3 domain, whereas their central regions contain binding sites for clathrin and for the clathrin adaptor AP-2. We have defined here amino acids of Amphiphysin 1 crucial for binding to AP-2 and clathrin. Overexpression in Chinese hamster ovary cells of an Amphiphysin 1 fragment that binds both AP-2 and clathrin resulted in a segregation of clathrin, which acquired a diffuse distribution, from AP-2, which accumulated at patches also positive for Eps15. These effects correlated with a block in clathrin-mediated endocytosis. A fragment selectively interacting with clathrin produced a similar effect. These results can be explained by the binding of Amphiphysin to the NH2-terminal domain of clathrin and by a competition with the binding of this domain to the β-subunit of AP-2 and AP180. The interaction of Amphiphysin 1 with either clathrin or AP-2 did not prevent its interaction with dynamin, supporting the existence of tertiary complexes between these proteins. Together with previous evidence indicating a direct interaction between Amphiphysin and membrane lipids, these findings support a model in which Amphiphysin acts as a multifunctional adaptor linking the membrane to coat proteins and coat proteins to dynamin and synaptojanin.

  • anti Amphiphysin i antibodies in patients with paraneoplastic neurological disorders associated with small cell lung carcinoma
    Journal of Neurology Neurosurgery and Psychiatry, 1999
    Co-Authors: Albert Saiz, Margaret H. Butler, Josep Dalmau, Q M Chen, J Y Delattre, P De Camilli, Francesc Graus
    Abstract:

    Patients with stiff man syndrome and breast cancer develop anti-Amphiphysin I antibodies that primarily recognise the C terminus of the protein. Anti-Amphiphysin I antibodies have also been identified in a few patients with paraneoplastic neurological disorders (PND) and small cell lung cancer (SCLC). The frequency of anti-Amphiphysin I antibodies in patients with SCLC and PND was analysed and the epitope specificity of these antibodies was characterised. Anti-Amphiphysin I antibodies were evaluated by immunohistochemistry on human and rat cerebellum and immunoblots of rat brain homogenates. Serum samples included 134 patients with PND and anti-Hu antibodies (83% had SCLC), 44 with SCLC and PND without anti-Hu-antibodies, 63 with PND and either Yo, Ri, or Tr antibodies, 146 with SCLC without PND, and 104 with non-PND. Positive serum samples were confirmed with immunoblots of recombinant human Amphiphysin I and immunoreacted with five overlapping peptide fragments covering the full length of the molecule. Serum samples positive for anti-Amphiphysin I antibodies included those from seven (2.9%) patients with PND and two (1.4%) with SCLC without PND. Six of the seven anti-Amphiphysin I antibody positive patients with PND had SCLC (three with Hu-antibodies), and one had anti-Hu-antibodies but no detectable tumour. The PND included encephalomyelitis/sensory neuropathy (five patients), cerebellar degeneration (one), and opsoclonus (one). All anti-Amphiphysin I antibodies reacted with the C terminus of Amphiphysin I, but seven also recognised other fragments of the molecule. In conclusion, anti-Amphiphysin I antibodies are present at low frequency in patients with SCLC irrespective of the presence of an associated PND. All anti-Amphiphysin I antibody positive serum samples have in common reactivity with the C terminus of the protein.

  • Amphiphysin ii sh3p9 bin1 a member of the Amphiphysin rvs family is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around t tubules in skeletal muscle
    Journal of Cell Biology, 1997
    Co-Authors: Margaret H. Butler, Detlev Grabs, Carol David, Laurie Daniell, Gian Carlo Ochoa, Zachary Freyberg, Ottavio Cremona, Pietro De Camilli
    Abstract:

    Amphiphysin (Amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man syndrome, is a neuronal protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. The yeast homologue of Amphiphysin, Rvs167, has pleiotropic functions, including a role in endocytosis and in actin dynamics, suggesting that Amphiphysin may also be implicated in the function of the presynaptic actin cytoskeleton. We report here the characterization of a second mammalian Amphiphysin gene, Amphiphysin II (SH3P9; BIN1), which encodes products primarily expressed in skeletal muscle and brain, as differentially spliced isoforms. In skeletal muscle, Amphiphysin II is concentrated around T tubules, while in brain it is concentrated in the cytomatrix beneath the plasmamembrane of axon initial segments and nodes of Ranvier. In both these locations, Amphiphysin II is colocalized with splice variants of ankyrin3 (ankyrinG), a component of the actin cytomatrix. In the same regions, the presence of clathrin has been reported. These findings support the hypothesis that, even in mammalian cells, Amphiphysin/Rvs family members have a role both in endocytosis and in actin function and suggest that distinct Amphiphysin isoforms contribute to define distinct domains of the cortical cytoplasm. Since Amphiphysin II (BIN1) was reported to interact with Myc, it may also be implicated in a signaling pathway linking the cortical cytoplasm to nuclear function.

Carol David - One of the best experts on this subject based on the ideXlab platform.

  • Amphiphysin II (SH3P9; BIN1), a Member of the Amphiphysin/Rvs Family, Is Concentrated in the Cortical Cytomatrix of Axon Initial Segments and Nodes of Ranvier in Brain and around T Tubules in Skeletal Muscle
    2013
    Co-Authors: Margaret Husta Butler, Detlev Grabs, Carol David, Laurie Daniell, Gian Carlo Ochoa, Zachary Freyberg, Ottavio Cremona, Pietro De Camilli
    Abstract:

    Abstract. Amphiphysin (Amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man syndrome, is a neuronal protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. The yeast homologue of Amphiphysin, Rvs167, has pleiotropic functions, including a role in endocytosis and in actin dynamics, suggesting that Amphiphysin may also be implicated in the function of the presynaptic actin cytoskeleton. We report here the characterization of a second mammalian Amphiphysin gene, Amphiphysin II (SH3P9; BIN1), which encodes products primarily expressed in skeletal muscle and brain, as differentially spliced isoforms. In skeletal muscle, Amphiphysin II is concentrated around T tubules, while in brain it is concentrated in the cytomatrix beneath the plasmamembran

  • Molecular Medicine @ 1998 The Picower Institute Press Expression of Amphiphysin I, an Autoantigen of Paraneoplastic Neurological Syndromes, in Breast Cancer
    2012
    Co-Authors: Scott Floyd, Carol David, Michele Solimena, Zachary Freyberg, Ottavio Cremona, Margaret Husta Butler, Xiaomei Zhang, Akira A Tokunaga, Hideki Ishizu, Kimiko Tsutsui
    Abstract:

    Amphiphysin I is a 128 kD protein highly concentrated in nerve tenminals, where it has a putative role in endocytosis. It is a dominant autoantigen in patients with stiff-man syndrome associated with breast cancer, as well as in other paraneoplastic autoimmune neurological disorders. To elucidate the connection between Amphiphysin I autoimmunity and cancer, we investigated its expression in breast cancer tissue. We report that Amphiphysin I was expressed as two isoforms of 128 and 108 kD in the breast cancer of a patient with anti-Amphiphysin I antibodies and paraneoplastic sensory neuronopathy. Amphiphysin I was also detectable at vari-able levels in several other human breast cancer tissues and cell lines and at low levels in normal mammary tissue and a variety of other non-neuronal tissues. The predominant Amphiphysin I isoform expressed outside the brain in humans is the 108 kD isoform which represents an altematively spliced variant of neuronal Amphiphysin I missing a 42 amino acid insert. Our study suggests a link between Amphiphysin I expression in cancer and Amphiphysin I autoimmunity. The enhanced expression of Amphiphysin I in some forms of cancer supports the hypothesis that Amphiphysin family members may play a role in the biology of cancer cells

  • Amphiphysin I Antisense Oligonucleotides Inhibit Neurite Outgrowth in Cultured Hippocampal Neurons
    The Journal of Neuroscience, 1998
    Co-Authors: Olaf Mundigl, Vladimir I. Slepnev, Carol David, Gian Carlo Ochoa, Alexander V Kabanov, Pietro De Camilli
    Abstract:

    Amphiphysin I is an SH3 domain-containing neuronal protein, enriched in axon terminals, which was reported to act as a physiological binding partner for dynamin I in synaptic vesicle endocytosis. Rvs167 and Rvs161, the yeast homologs of Amphiphysin I, have been implicated in endocytosis, actin function, and cell polarity. Now we have explored the possibility that Amphiphysin I also may have a role in actin dynamics and cell polarity by testing the effect of Amphiphysin I suppression on neurite outgrowth. Freshly plated hippocampal neurons were exposed to antisense oligonucleotides via a new delivery system based on a polycationic amphipathic polymer, PS980. Western blot analysis revealed that Amphiphysin I levels steadily increased with neuronal differentiation, whereas in antisense-treated cultures Amphiphysin I levels were reduced to ∼10% of control levels at 48 hr. Concomitantly, a collapse of growth cones and a severe inhibition of neurite outgrowth and axon formation were observed. A similar effect was observed previously after dynamin I suppression in the same culture system (Torre et al., 1994). We also have found that Amphiphysin I and dynamin I colocalize in developing neurons at all developmental stages and that a pool of both proteins is colocalized with actin patches at the leading edge of growth cones. Our findings suggest a conserved role of the Amphiphysin protein family in the dynamics of the cortical cell cytoskeleton and provide new evidence for a close functional link between Amphiphysin I and dynamin I.

  • Expression of Amphiphysin I, an Autoantigen of Paraneoplastic Neurological Syndromes, in Breast Cancer
    Molecular Medicine, 1998
    Co-Authors: Scott Floyd, Carol David, Michele Solimena, Zachary Freyberg, Ottavio Cremona, Margaret Husta Butler, Xiaomei Zhang, Hideki Ishizu, Akira Tokunaga, Kimiko Tsutsui
    Abstract:

    Amphiphysin I is a 128 kD protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. It is a dominant autoantigen in patients with stiff-man syndrome associated with breast cancer, as well as in other paraneoplastic autoimmune neurological disorders. To elucidate the connection between Amphiphysin I autoimmunity and cancer, we investigated its expression in breast cancer tissue. We report that Amphiphysin I was expressed as two isoforms of 128 and 108 kD in the breast cancer of a patient with anti-Amphiphysin I antibodies and paraneoplastic sensory neuronopathy. Amphiphysin I was also detectable at variable levels in several other human breast cancer tissues and cell lines and at low levels in normal mammary tissue and a variety of other non-neuronal tissues. The predominant Amphiphysin I isoform expressed outside the brain in humans is the 108 kD isoform which represents an alternatively spliced variant of neuronal Amphiphysin I missing a 42 amino acid insert. Our study suggests a link between Amphiphysin I expression in cancer and Amphiphysin I autoimmunity. The enhanced expression of Amphiphysin I in some forms of cancer supports the hypothesis that Amphiphysin family members may play a role in the biology of cancer cells.

  • Amphiphysin ii sh3p9 bin1 a member of the Amphiphysin rvs family is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around t tubules in skeletal muscle
    Journal of Cell Biology, 1997
    Co-Authors: Margaret H. Butler, Detlev Grabs, Carol David, Laurie Daniell, Gian Carlo Ochoa, Zachary Freyberg, Ottavio Cremona, Pietro De Camilli
    Abstract:

    Amphiphysin (Amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man syndrome, is a neuronal protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. The yeast homologue of Amphiphysin, Rvs167, has pleiotropic functions, including a role in endocytosis and in actin dynamics, suggesting that Amphiphysin may also be implicated in the function of the presynaptic actin cytoskeleton. We report here the characterization of a second mammalian Amphiphysin gene, Amphiphysin II (SH3P9; BIN1), which encodes products primarily expressed in skeletal muscle and brain, as differentially spliced isoforms. In skeletal muscle, Amphiphysin II is concentrated around T tubules, while in brain it is concentrated in the cytomatrix beneath the plasmamembrane of axon initial segments and nodes of Ranvier. In both these locations, Amphiphysin II is colocalized with splice variants of ankyrin3 (ankyrinG), a component of the actin cytomatrix. In the same regions, the presence of clathrin has been reported. These findings support the hypothesis that, even in mammalian cells, Amphiphysin/Rvs family members have a role both in endocytosis and in actin function and suggest that distinct Amphiphysin isoforms contribute to define distinct domains of the cortical cytoplasm. Since Amphiphysin II (BIN1) was reported to interact with Myc, it may also be implicated in a signaling pathway linking the cortical cytoplasm to nuclear function.