Computer modeling of synapsin I binding to synaptic vesicles and F-actin: Implications for regulation of neurotransmitter release

Fabio Benfenati, Flavia Valtorta, Paul Greengard

Research output: Contribution to journalArticle

Abstract

Synapsin I is a neuron-specific phosphoprotein that binds to small synaptic vesicles and actin filaments in a phosphorylation-dependent fashion. It has been hypothesized that dephosphorylated synapsin I inhibits neurotransmitter release either by forming a cage around synaptic vesicles (cage model) or by anchoring them to the F-actin cytoskeleton of the nerve terminal (crosslinking model). Computer modeling was performed with the aim of testing the impact of phosphorylation on the molecular interactions of synapsin I within the nerve terminal. The results of the simulation experiments demonstrate that in the crosslinking model the phosphorylation of synapsin I causes a severalfold increase in the number of vesicles released from the cytoskeleton and that in the cage model the phosphorylation induces a 2-fold increase in the number of vesicles bearing one or more unsaturated synapsin I binding sites. These data are compatible with the view that the function of synapsin I in the short-term regulation of neurotransmitter release is to induce a phosphorylation-dependent transition of synaptic vesicles from a "reserve pool" to a readily "releasable pool" of vesicles.

Original languageEnglish
Pages (from-to)575-579
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number2
Publication statusPublished - 1991

Fingerprint

Synapsins
Synaptic Vesicles
Neurotransmitter Agents
Actins
Phosphorylation
Actin Cytoskeleton
Phosphoproteins
Cytoskeleton
Binding Sites
Neurons

Keywords

  • Cytoskeleton
  • Exocytosis
  • Nerve terminal
  • Protein phosphorylation

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

@article{ecd27bf526844befbcb1f83bcb17db91,
title = "Computer modeling of synapsin I binding to synaptic vesicles and F-actin: Implications for regulation of neurotransmitter release",
abstract = "Synapsin I is a neuron-specific phosphoprotein that binds to small synaptic vesicles and actin filaments in a phosphorylation-dependent fashion. It has been hypothesized that dephosphorylated synapsin I inhibits neurotransmitter release either by forming a cage around synaptic vesicles (cage model) or by anchoring them to the F-actin cytoskeleton of the nerve terminal (crosslinking model). Computer modeling was performed with the aim of testing the impact of phosphorylation on the molecular interactions of synapsin I within the nerve terminal. The results of the simulation experiments demonstrate that in the crosslinking model the phosphorylation of synapsin I causes a severalfold increase in the number of vesicles released from the cytoskeleton and that in the cage model the phosphorylation induces a 2-fold increase in the number of vesicles bearing one or more unsaturated synapsin I binding sites. These data are compatible with the view that the function of synapsin I in the short-term regulation of neurotransmitter release is to induce a phosphorylation-dependent transition of synaptic vesicles from a {"}reserve pool{"} to a readily {"}releasable pool{"} of vesicles.",
keywords = "Cytoskeleton, Exocytosis, Nerve terminal, Protein phosphorylation",
author = "Fabio Benfenati and Flavia Valtorta and Paul Greengard",
year = "1991",
language = "English",
volume = "88",
pages = "575--579",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "2",

}

TY - JOUR

T1 - Computer modeling of synapsin I binding to synaptic vesicles and F-actin

T2 - Implications for regulation of neurotransmitter release

AU - Benfenati, Fabio

AU - Valtorta, Flavia

AU - Greengard, Paul

PY - 1991

Y1 - 1991

N2 - Synapsin I is a neuron-specific phosphoprotein that binds to small synaptic vesicles and actin filaments in a phosphorylation-dependent fashion. It has been hypothesized that dephosphorylated synapsin I inhibits neurotransmitter release either by forming a cage around synaptic vesicles (cage model) or by anchoring them to the F-actin cytoskeleton of the nerve terminal (crosslinking model). Computer modeling was performed with the aim of testing the impact of phosphorylation on the molecular interactions of synapsin I within the nerve terminal. The results of the simulation experiments demonstrate that in the crosslinking model the phosphorylation of synapsin I causes a severalfold increase in the number of vesicles released from the cytoskeleton and that in the cage model the phosphorylation induces a 2-fold increase in the number of vesicles bearing one or more unsaturated synapsin I binding sites. These data are compatible with the view that the function of synapsin I in the short-term regulation of neurotransmitter release is to induce a phosphorylation-dependent transition of synaptic vesicles from a "reserve pool" to a readily "releasable pool" of vesicles.

AB - Synapsin I is a neuron-specific phosphoprotein that binds to small synaptic vesicles and actin filaments in a phosphorylation-dependent fashion. It has been hypothesized that dephosphorylated synapsin I inhibits neurotransmitter release either by forming a cage around synaptic vesicles (cage model) or by anchoring them to the F-actin cytoskeleton of the nerve terminal (crosslinking model). Computer modeling was performed with the aim of testing the impact of phosphorylation on the molecular interactions of synapsin I within the nerve terminal. The results of the simulation experiments demonstrate that in the crosslinking model the phosphorylation of synapsin I causes a severalfold increase in the number of vesicles released from the cytoskeleton and that in the cage model the phosphorylation induces a 2-fold increase in the number of vesicles bearing one or more unsaturated synapsin I binding sites. These data are compatible with the view that the function of synapsin I in the short-term regulation of neurotransmitter release is to induce a phosphorylation-dependent transition of synaptic vesicles from a "reserve pool" to a readily "releasable pool" of vesicles.

KW - Cytoskeleton

KW - Exocytosis

KW - Nerve terminal

KW - Protein phosphorylation

UR - http://www.scopus.com/inward/record.url?scp=0026069564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026069564&partnerID=8YFLogxK

M3 - Article

C2 - 1671174

AN - SCOPUS:0026069564

VL - 88

SP - 575

EP - 579

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 2

ER -