Open AccessLysophosphatidylcholine inhibits membrane‐associated SNARE complex disassembly
Author(s) -
Shin Leah,
Wang Sunxi,
Lee JinSook,
Flack Amanda,
Mao Guangzhao,
Jena Bhanu P.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01433.x
Subject(s) - snare complex , lysophosphatidylcholine , snap25 , microbiology and biotechnology , lipid bilayer fusion , vesicle fusion , biology , synaptotagmin 1 , membrane curvature , synaptic vesicle , vesicle , exocytosis , secretion , membrane protein , chemistry , membrane , biochemistry , phosphatidylcholine , phospholipid
In cells, N ‐ethylmaleimide‐sensitive factor (NSF) attachment protein receptors called SNAREs are involved in membrane fusion. In neurons, for example, target membrane proteins SNAP‐25 and syntaxin called t‐SNAREs present at the pre‐synaptic membrane, and a synaptic vesicle‐associated membrane protein (VAMP) or v‐SNARE, is part of the conserved protein complex involved in neurotransmission. Cholesterol and LPC (L‐α‐lysophosphatidylcholine) are known to contribute to the negative and positive curvature respectively of membranes. In this study, using purified recombinant neuronal membrane‐associated SNAREs, we demonstrate for the first time that membrane‐curvature‐influencing lipids profoundly influence SNARE complex disassembly. Exposure of cholesterol‐associated t‐SNARE and v‐SNARE liposome mixtures to NSF–ATP results in dissociated vesicles. In contrast, exposure of LPC‐associated t‐SNARE and v‐SNARE liposome mixtures to NSF–ATP, results in inhibition of t‐/v‐SNARE disassembly and the consequent accumulation of clustered vesicles. Similarly, exposure of isolated rat brain slices and pancreas to cholesterol or LPC, also demonstrates LPC‐induced inhibition of SNARE complex disassembly. Earlier studies demonstrate a strong correlation between altered plasma LPC levels and cancer. The altered plasma LPC levels observed in various cancers may in part contribute to defects in SNARE assembly–disassembly and membrane fusion, consequently affecting protein maturation and secretion in cancer cells.