Palmitoylation of the synaptic vesicle fusion machinery.
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.
Prescott
Gerald R
GR
Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Gorleku
Oforiwa A
OA
Greaves
Jennifer
J
Chamberlain
Luke H
LH
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D006801:Humans; D054878:Lipoylation / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D050600:SNARE Proteins / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D050857:Synaptotagmins / Q000378:metabolism
D008565:Membrane Proteins; D050600:SNARE Proteins; D050857:Synaptotagmins