title: Lysophosphatidylcholine inhibits membrane-associated SNARE complex disassembly.
abstract: 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.
authors: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors: Leah
authors: L
authors: Shin
authors: Sunxi
authors: S
authors: Wang
authors: Jin-Sook
authors: JS
authors: Lee
authors: Amanda
authors: A
authors: Flack
authors: Guangzhao
authors: G
authors: Mao
authors: Bhanu P
authors: BP
authors: Jena
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D008027:Light; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D018625:Microscopy, Atomic Force; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism; D011510:Proteolipids / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D050600:SNARE Proteins / Q000378:metabolism*; D012542:Scattering, Radiation; D053835:Unilamellar Liposomes / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D008244:Lysophosphatidylcholines; D011510:Proteolipids; D050600:SNARE Proteins; D053835:Unilamellar Liposomes; C020485:proteoliposomes; D000255:Adenosine Triphosphate; D002784:Cholesterol; D052066:N-Ethylmaleimide-Sensitive Proteins