Palmitoylation of the synaptic vesicle fusion machinery

Gerald R Prescott, Oforiwa A Gorleku, Jennifer Greaves, Luke H Chamberlain

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

The fusion of synaptic vesicles with the pre-synaptic plasma membrane mediates the secretion of neurotransmitters at nerve terminals. This pathway is regulated by an array of protein-protein interactions. Of central importance are the soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor (SNARE) proteins syntaxin 1 and SNAP25, which are associated with the pre-synaptic plasma membrane and vesicle-associated membrane protein (VAMP2), a synaptic vesicle SNARE. Syntaxin 1, SNAP25 and VAMP2 interact to form a tight complex bridging the vesicle and plasma membranes, which has been suggested to represent the minimal membrane fusion machinery. Synaptic vesicle fusion is stimulated by a rise in intraterminal Ca2+ levels, and a major Ca2+ sensor for vesicle fusion is synaptotagmin I. Synaptotagmin is likely to couple Ca2+ entry to vesicle fusion via Ca2+-dependent and independent interactions with membrane phospholipids and the SNARE proteins. Intriguingly, syntaxin 1, SNAP25, VAMP2 and synaptotagmin I have all been reported to be modified by palmitoylation in neurons. In this review, we discuss the mechanisms and dynamics of palmitoylation of these proteins and speculate on how palmitoylation might contribute to the regulation of synaptic vesicle fusion.

Original languageEnglish
Pages (from-to)1135-1149
Number of pages15
JournalJournal of Neurochemistry
Volume110
Issue number4
DOIs
Publication statusPublished - 21 Jul 2009

Fingerprint

Lipoylation
Synaptic Vesicles
Vesicle-Associated Membrane Protein 2
Machinery
Syntaxin 1
Fusion reactions
N-Ethylmaleimide-Sensitive Proteins
Synaptotagmin I
Cell membranes
Synaptic Membranes
Cell Membrane
Proteins
R-SNARE Proteins
Synaptotagmins
SNARE Proteins
Protein Array Analysis
Membrane Fusion
Membranes
Neurotransmitter Agents
Phospholipids

Keywords

  • Animals
  • Calcium Signaling
  • Humans
  • Lipoylation
  • Membrane Fusion
  • Membrane Proteins
  • Presynaptic Terminals
  • SNARE Proteins
  • Synaptic Membranes
  • Synaptic Transmission
  • Synaptic Vesicles
  • Synaptotagmins
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review

Cite this

Palmitoylation of the synaptic vesicle fusion machinery. / Prescott, Gerald R; Gorleku, Oforiwa A; Greaves, Jennifer; Chamberlain, Luke H.

In: Journal of Neurochemistry, Vol. 110, No. 4, 21.07.2009, p. 1135-1149.

Research output: Contribution to journalReview article

Prescott, Gerald R ; Gorleku, Oforiwa A ; Greaves, Jennifer ; Chamberlain, Luke H. / Palmitoylation of the synaptic vesicle fusion machinery. In: Journal of Neurochemistry. 2009 ; Vol. 110, No. 4. pp. 1135-1149.
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N2 - The fusion of synaptic vesicles with the pre-synaptic plasma membrane mediates the secretion of neurotransmitters at nerve terminals. This pathway is regulated by an array of protein-protein interactions. Of central importance are the soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor (SNARE) proteins syntaxin 1 and SNAP25, which are associated with the pre-synaptic plasma membrane and vesicle-associated membrane protein (VAMP2), a synaptic vesicle SNARE. Syntaxin 1, SNAP25 and VAMP2 interact to form a tight complex bridging the vesicle and plasma membranes, which has been suggested to represent the minimal membrane fusion machinery. Synaptic vesicle fusion is stimulated by a rise in intraterminal Ca2+ levels, and a major Ca2+ sensor for vesicle fusion is synaptotagmin I. Synaptotagmin is likely to couple Ca2+ entry to vesicle fusion via Ca2+-dependent and independent interactions with membrane phospholipids and the SNARE proteins. Intriguingly, syntaxin 1, SNAP25, VAMP2 and synaptotagmin I have all been reported to be modified by palmitoylation in neurons. In this review, we discuss the mechanisms and dynamics of palmitoylation of these proteins and speculate on how palmitoylation might contribute to the regulation of synaptic vesicle fusion.

AB - The fusion of synaptic vesicles with the pre-synaptic plasma membrane mediates the secretion of neurotransmitters at nerve terminals. This pathway is regulated by an array of protein-protein interactions. Of central importance are the soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor (SNARE) proteins syntaxin 1 and SNAP25, which are associated with the pre-synaptic plasma membrane and vesicle-associated membrane protein (VAMP2), a synaptic vesicle SNARE. Syntaxin 1, SNAP25 and VAMP2 interact to form a tight complex bridging the vesicle and plasma membranes, which has been suggested to represent the minimal membrane fusion machinery. Synaptic vesicle fusion is stimulated by a rise in intraterminal Ca2+ levels, and a major Ca2+ sensor for vesicle fusion is synaptotagmin I. Synaptotagmin is likely to couple Ca2+ entry to vesicle fusion via Ca2+-dependent and independent interactions with membrane phospholipids and the SNARE proteins. Intriguingly, syntaxin 1, SNAP25, VAMP2 and synaptotagmin I have all been reported to be modified by palmitoylation in neurons. In this review, we discuss the mechanisms and dynamics of palmitoylation of these proteins and speculate on how palmitoylation might contribute to the regulation of synaptic vesicle fusion.

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KW - Synaptic Transmission

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