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Christian Rosenmund - One of the best experts on this subject based on the ideXlab platform.
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additive effects on the Energy Barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate
eLife, 2015Co-Authors: Sebastiaan Schotten, Marieke Meijer, Alexander M Walter, Vincent Huson, Lauren Mamer, Lawrence Kalogreades, Mirelle Ter Veer, Marvin Ruiter, Nils Brose, Christian RosenmundAbstract:The Energy required to fuse synaptic vesicles with the plasma membrane (‘activation Energy’) is considered a major determinant in synaptic efficacy. From reaction rate theory, we predict that a class of modulations exists, which utilize linear modulation of the Energy Barrier for fusion to achieve supralinear effects on the fusion rate. To test this prediction experimentally, we developed a method to assess the number of releasable vesicles, rate constants for vesicle priming, unpriming, and fusion, and the activation Energy for fusion by fitting a vesicle state model to synaptic responses induced by hypertonic solutions. We show that complexinI/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive vs multiplicative relationship between activation Energy and fusion rate provides a novel explanation for previously observed non-linear effects of genetic/pharmacological perturbations on synaptic transmission and a novel interpretation of the cooperative nature of Ca2+-dependent release. DOI: http://dx.doi.org/10.7554/eLife.05531.001
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Activation of metabotropic GABA receptors increases the Energy Barrier for vesicle fusion.
Journal of cell science, 2011Co-Authors: Benjamin R Rost, Christian Rosenmund, Patrick Nicholson, Gudrun Ahnert-hilger, Andreas Rummel, Joerg Breustedt, Dietmar SchmitzAbstract:Neurotransmitter release from presynaptic terminals is under the tight control of various metabotropic receptors. We report here that in addition to the regulation of Ca(2+) channel activity, metabotropic GABA(B) receptors (GABA(B)Rs) at murine hippocampal glutamatergic synapses utilize an inhibitory pathway that directly targets the synaptic vesicle release machinery. Acute application of the GABA(B)R agonist baclofen rapidly and reversibly inhibits vesicle fusion, which occurs independently of the SNAP-25 C-terminus. Using applications of hypertonic sucrose solutions, we find that the size of the readily releasable pool remains unchanged by GABA(B)R activation, but the sensitivity of primed vesicles to hypertonic stimuli appears lowered as the response amplitudes at intermediate sucrose concentrations are smaller and release kinetics are slowed. These data show that presynaptic GABA(B)Rs can inhibit neurotransmitter release directly by increasing the Energy Barrier for vesicle fusion.
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munc13 1 c1 domain activation lowers the Energy Barrier for synaptic vesicle fusion
The Journal of Neuroscience, 2007Co-Authors: Jayeeta Basu, Nils Brose, Andrea Betz, Christian RosenmundAbstract:Synapses need to encode a wide dynamic range of action potential frequencies. Essential vesicle priming proteins of the Munc13 (mammalian Unc13) family play an important role in adapting vesicle supply to variable demand and thus influence short-term plasticity characteristics and synaptic function. Structure–function analyses of Munc13s have identified a “catalytic” C-terminal domain and several N-terminal modulatory domains, including a diacylglycerol/phorbol ester [4β-phorbol-12, 13-dibutyrate (PDBu)] binding C1 domain. Although still allowing basal priming, a Munc13-1 C1 domain mutation (H567K) prevents PDBu induced potentiation of evoked transmitter release, leads to strong depression during trains of synaptic activity, and causes perinatal lethality in mice. To understand the mechanism of C1 domain-mediated modulation of Munc13 function, we examined how PDBu increases neurotransmitter release. Analyses of osmotically induced release as well as Ca2+ triggered and spontaneous release showed that PDBu increases the vesicular release rate without affecting the size of the readily releasable vesicle pool, linking C1 domain activation to a lowering of the Energy Barrier for vesicle fusion. PDBu binding-deficient mutant Munc13-1H567K synapses mirrored the vesicular release properties of PDBu-potentiated wild-type synapses, indicating that Munc13-1H567K is a gain-of-function mutant, which conformationally mimics the PDBu-activated state of Munc13-1. We propose a PKC analogous two-state model of regulation of Munc13s, in which the basal state of Munc13s is disinhibited by C1 domain activation into a state of facilitated vesicle release, regardless of whether the release is spontaneous or action potential triggered.
Masao Iwamatsu - One of the best experts on this subject based on the ideXlab platform.
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Free-Energy Barrier of Filling a Spherical Cavity in the Presence of Line Tension: Implication to the Energy Barrier between the Cassie and Wenzel States on a Superhydrophobic Surface with Spherical Cavities
Langmuir, 2016Co-Authors: Masao IwamatsuAbstract:The free-Energy Barrier of filling a spherical cavity having an inner wall of various wettabilities is studied. The morphology and free Energy of a lens-shaped droplet are determined from the minimum of the free Energy. The effect of line tension on the free Energy is also studied. Then, the equilibrium contact angle of the droplet is determined from the generalized Young’s equation. By increasing the droplet volume within the spherical cavity, the droplet morphology changes from spherical with an equilibrium contact angle of 180° to a lens with a convex meniscus, where the morphological complete drying transition occurs. By further increasing the droplet volume, the meniscus changes from convex to concave. Then, the lens-shaped droplet with concave meniscus spreads over the whole inner wall, resulting in an equilibrium contact angle of 0° to leave a spherical bubble, where the morphological complete wetting transition occurs. Finally, the whole cavity is filled with liquid. The free Energy shows a barrie...
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Free-Energy Barrier of filling a spherical cavity in the presence of line tension: Implication to the Energy Barrier between the Cassie and Wenzel state on a superhydrophobic surface with spherical cavities
arXiv: Soft Condensed Matter, 2016Co-Authors: Masao IwamatsuAbstract:The free-Energy Barrier of filling a spherical cavity having an inner wall of various wettabiities is studied. The morphology and free Energy of a lens-shaped droplet are determined from the minimum of the free Energy. The effect of line tension on the free Energy is also studied. Then, the equilibrium contact angle of the droplet is determined from the generalized Young's equation. By increasing the droplet volume within the spherical cavity, the droplet morphology changes from spherical with an equilibrium contact angle of $180^{\circ}$ to a lens with a convex meniscus, where the morphological complete drying transition occurs. By further increasing the droplet volume, the meniscus changes from convex to concave. Then, the lens-shaped droplet with concave meniscus spreads over the whole inner wall resulting in an equilibrium contact angle of $0^{\circ}$ to leave a spherical bubble, where the morphological complete wetting transition occurs. Finally, the whole cavity is filled with liquid. The free Energy shows a Barrier from complete drying to complete wetting as a function of droplet volume, which corresponds to the Energy Barrier between the Cassie and Wenzel state of the superhydrophobic surface with spherical cavities. The free-Energy maximum occurs when the meniscus of the droplet becomes flat and it is given by an analytic formula. The effect of line tension is expressed by the scaled line tension, and this effect is largest at the free-Energy maximum. The positive line tension increases the free-Energy maximum, which thus, increases the stability of the Cassie superhydrophobic state, whereas the negative line tension destabilizes the superhydrophobic state.
Sebastiaan Schotten - One of the best experts on this subject based on the ideXlab platform.
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additive effects on the Energy Barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate
eLife, 2015Co-Authors: Sebastiaan Schotten, Marieke Meijer, Alexander M Walter, Vincent Huson, Lauren Mamer, Lawrence Kalogreades, Mirelle Ter Veer, Marvin Ruiter, Nils Brose, Christian RosenmundAbstract:The Energy required to fuse synaptic vesicles with the plasma membrane (‘activation Energy’) is considered a major determinant in synaptic efficacy. From reaction rate theory, we predict that a class of modulations exists, which utilize linear modulation of the Energy Barrier for fusion to achieve supralinear effects on the fusion rate. To test this prediction experimentally, we developed a method to assess the number of releasable vesicles, rate constants for vesicle priming, unpriming, and fusion, and the activation Energy for fusion by fitting a vesicle state model to synaptic responses induced by hypertonic solutions. We show that complexinI/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive vs multiplicative relationship between activation Energy and fusion rate provides a novel explanation for previously observed non-linear effects of genetic/pharmacological perturbations on synaptic transmission and a novel interpretation of the cooperative nature of Ca2+-dependent release. DOI: http://dx.doi.org/10.7554/eLife.05531.001
Dietmar Schmitz - One of the best experts on this subject based on the ideXlab platform.
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Activation of metabotropic GABA receptors increases the Energy Barrier for vesicle fusion.
Journal of cell science, 2011Co-Authors: Benjamin R Rost, Christian Rosenmund, Patrick Nicholson, Gudrun Ahnert-hilger, Andreas Rummel, Joerg Breustedt, Dietmar SchmitzAbstract:Neurotransmitter release from presynaptic terminals is under the tight control of various metabotropic receptors. We report here that in addition to the regulation of Ca(2+) channel activity, metabotropic GABA(B) receptors (GABA(B)Rs) at murine hippocampal glutamatergic synapses utilize an inhibitory pathway that directly targets the synaptic vesicle release machinery. Acute application of the GABA(B)R agonist baclofen rapidly and reversibly inhibits vesicle fusion, which occurs independently of the SNAP-25 C-terminus. Using applications of hypertonic sucrose solutions, we find that the size of the readily releasable pool remains unchanged by GABA(B)R activation, but the sensitivity of primed vesicles to hypertonic stimuli appears lowered as the response amplitudes at intermediate sucrose concentrations are smaller and release kinetics are slowed. These data show that presynaptic GABA(B)Rs can inhibit neurotransmitter release directly by increasing the Energy Barrier for vesicle fusion.
Max L Berkowitz - One of the best experts on this subject based on the ideXlab platform.
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free Energy Barrier for melittin reorientation from a membrane bound state to a transmembrane state
Journal of Physical Chemistry B, 2013Co-Authors: Sheeba Jem Irudayam, Tobias Pobandt, Max L BerkowitzAbstract:An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. Experiments measure the fraction of peptides in the surface state and the transmembrane state, but no computational study exists that quantifies the free Energy curve for the reorientation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight in understanding the peptide-lipid properties that influence the existence of the free Energy Barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free Energy Barrier is reduced when the P/L ratio increases. In addition, we study the cooperative effect; specifically we investigate if the reorientation Barrier is smaller for a second melittin, given that another neighbo...
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free Energy Barrier for melittin reorientation from a membrane bound state to a transmembrane state
arXiv: Biological Physics, 2013Co-Authors: Sheeba Jem Irudayam, Tobias Pobandt, Max L BerkowitzAbstract:An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free Energy Barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free Energy Barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the Barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the Barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect.