Cholesterol and synaptic vesicle exocytosis.
LIPIDS MAY AFFECT SYNAPTIC FUNCTION IN AT LEAST TWO WAYS: by acting as ligands for effector proteins [e.g., phosphatidylinositol (4,5) bisphosphate, diacylglycerol-mediated signaling] or by modifying the physicochemical properties and molecular organization of synaptic membranes. One that acts in the latter manner is cholesterol, an essential structural component of plasma membranes that is largely enriched in the membranes of synapses and synaptic vesicles, in which it may be involved in lipid-lipid and protein-lipid interactions. Cholesterol is an important constituent of the "membrane rafts" that may play a role in recruiting and organizing the specific proteins of the exocytic pathways. Furthermore, many synaptic proteins bind directly to cholesterol. The regulation of cholesterol and lipid levels may therefore influence the specific interactions and activity of synaptic proteins, and have a strong impact on synaptic functions.
Rosa
Patrizia
P
CNR-Institute of Neuroscience and Department of Medical Pharmacology; University of Milan; Milan, Italy.
Fratangeli
Alessandra
A
Proc Natl Acad Sci U S A. 2001 May 8;98(10):5619-24
11331757
Nature. 1998 Jul 9;394(6689):192-5
9671304
Handb Exp Pharmacol. 2008;(184):1-21
18064409
J Physiol. 2007 Dec 15;585(Pt 3):693-8
17478530
Cell. 2006 Nov 17;127(4):831-46
17110340
J Physiol. 2006 Feb 15;571(Pt 1):83-99
16339182
J Physiol. 2007 Mar 1;579(Pt 2):413-29
17170046
J Cell Sci. 2010 Feb 15;123(Pt 4):595-605
20103534
EMBO J. 2001 May 1;20(9):2202-13
11331586
Nat Cell Biol. 2000 Jan;2(1):42-9
10620806
Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5141-6
19251653
J Biol Chem. 2004 Feb 13;279(7):5127-34
14660672