Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

Sebastiaan Schotten; Marieke Meijer; Alexander Matthias Walter; Vincent Huson; Lauren Mamer; Lawrence Kalogreades; Mirelle Ter Veer; Marvin Ruiter; Nils Brose; Christian Rosenmund; Jakob Balslev Sørensen; Matthijs Verhage; Lennart Niels Cornelisse

doi:10.7554/eLife.05531

Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

Sebastiaan Schotten, Marieke Meijer, Alexander Matthias Walter, Vincent Huson, Lauren Mamer, Lawrence Kalogreades, Mirelle Ter Veer, Marvin Ruiter, Nils Brose, Christian Rosenmund, Jakob Balslev Sørensen, Matthijs Verhage, Lennart Niels Cornelisse

Neuronal Signalling

27 Citationer (Scopus)

Abstract

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 Complexinl/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive versus 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.

Originalsprog	Engelsk
Artikelnummer	e05531
Tidsskrift	eLife
Vol/bind	4
Sider (fra-til)	1-25
Antal sider	25
ISSN	2050-084X
DOI	https://doi.org/10.7554/eLife.05531
Status	Udgivet - 14 apr. 2015

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10.7554/eLife.05531Licens: CC BY

Citationsformater

Schotten, S., Meijer, M., Walter, A. M., Huson, V., Mamer, L., Kalogreades, L., Ter Veer, M., Ruiter, M., Brose, N., Rosenmund, C., Sørensen, J. B., Verhage, M., & Cornelisse, L. N. (2015). Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate. eLife, 4, 1-25. Artikel e05531. https://doi.org/10.7554/eLife.05531

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title = "Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate",

abstract = "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 Complexinl/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive versus 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.",

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AU - Schotten, Sebastiaan

AU - Meijer, Marieke

AU - Walter, Alexander Matthias

AU - Huson, Vincent

AU - Mamer, Lauren

AU - Kalogreades, Lawrence

AU - Ter Veer, Mirelle

AU - Ruiter, Marvin

AU - Brose, Nils

AU - Rosenmund, Christian

AU - Sørensen, Jakob Balslev

AU - Verhage, Matthijs

AU - Cornelisse, Lennart Niels

PY - 2015/4/14

Y1 - 2015/4/14

N2 - 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 Complexinl/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive versus 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.

AB - 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 Complexinl/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive versus 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.

U2 - 10.7554/eLife.05531

DO - 10.7554/eLife.05531

M3 - Journal article

C2 - 25871846

SN - 2050-084X

VL - 4

SP - 1

EP - 25

JO - eLife

JF - eLife

M1 - e05531

ER -

Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

Abstract

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