Neuronal fusion pore assembly requires membrane cholesterol.
Cholesterol has been proposed to play a critical role in regulating neurotransmitter release and synaptic plasticity. The neuronal porosome/fusion pore, the secretory machinery at the nerve terminal, is a 12-17 nm cup-shaped lipoprotein structure composed of cholesterol and a number of proteins, among them calcium channels, and the t-SNARE proteins Syntaxin-1 and SNAP-25. During neurotransmission, synaptic vesicles dock and fuse at the porosome via interaction of their v-SNARE protein with t-SNAREs at the porosome base. Membrane-associated neuronal t-SNAREs interact in a circular array with liposome-associated neuronal v-SNARE to form the t-/v-SNARE ring complex. The SNARE complex along with calcium is required for the establishment of continuity between opposing bilayers. Here we show that although cholesterol is an integral component of the neuronal porosome and is required for maintaining its physical integrity and function, it has no influence on the conformation of the SNARE ring complex.
Cho
Won Jin
WJ
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
Jeremic
Aleksandar
A
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
Jin
Huan
H
Department of Biochemistry and Biophysics, University of California SanFrancisco, SanFrancisco, CA 94158, USA.
Ren
Gang
G
Department of Biochemistry and Biophysics, University of California SanFrancisco, SanFrancisco, CA 94158, USA.
Jena
Bhanu P
BP
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D018272:Porins / Q000378:metabolism* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism* / Q000648:ultrastructure; D013574:Synaptosomes / Q000737:chemistry
D018272:Porins; D050600:SNARE Proteins; D002784:Cholesterol
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