Leabu M
Department of Cellular and Molecular Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
J Cell Mol Med. 2006 Apr-Jun;10(2):423-7. doi: 10.1111/j.1582-4934.2006.tb00409.x.
Membrane fusion is a sine qua non process for cell physiology. It is critical for membrane biogenesis, intracellular traffic, and cell secretion. Although investigated for over a century, only in the last 15 years, the molecular machinery and mechanism of membrane fusion has been deciphered. The membrane fusion event elicits essentially three actors on stage: anionic phospholipids - phosphatidylinositols, phosphatidyl serines, specific membrane proteins, and the calcium ions, all participating in a well orchestrated symphony. Three soluble N-ethylmaleimide-sensitive factor (NSF)-attachment protein receptors (SNAREs) have been implicated in membrane fusion. Target membrane proteins, SNAP-25 and syntaxin (t- SNARE) and secretory vesicle-associated membrane protein (v-SNARE) or VAMPwere discovered in the 1990's and suggested to be the minimal fusion machinery. Subsequently, the molecular mechanism of SNARE-induced membrane fusion was discovered. It was demonstrated that when t-SNARE-associated lipid membrane is exposed to v-SNARE-associated vesicles in the presence of Ca(2+), the SNARE proteins interact in a circular array to form conducting channels, thus establishing continuity between the opposing bilayers. Further it was proved that SNAREs bring opposing bilayers close to within a distance of 2-3 Angstroms, allowing Ca(2+) to bridge them. The bridging of bilayers by Ca(2+) then leads to the expulsion of water between the bilayers at the contact site, allowing lipid mixing and membrane fusion. Calcium bridging of opposing bilayers leads to the release of water, both from the water shell of hydrated Ca(2+) ions, as well as the displacement of loosely coordinated water at the phosphate head groups in the lipid membrane. These discoveries provided for the first time, the molecular mechanism of SNARE-induced membrane fusion in cells. Some of the seminal discoveries are briefly discussed in this minireview.
膜融合是细胞生理学中必不可少的过程。它对于膜生物发生、细胞内运输和细胞分泌至关重要。尽管已经研究了一个多世纪，但直到最近15年，膜融合的分子机制才被破解。膜融合事件主要涉及三个关键因素：阴离子磷脂——磷脂酰肌醇、磷脂酰丝氨酸、特定的膜蛋白以及钙离子，它们共同参与一场精心编排的“交响乐”。三种可溶性N - 乙基马来酰亚胺敏感因子（NSF）附着蛋白受体（SNARE）与膜融合有关。靶膜蛋白、SNAP - 25和 syntaxin（t - SNARE）以及分泌囊泡相关膜蛋白（v - SNARE）或VAMP在20世纪90年代被发现，并被认为是最小的融合机制。随后，发现了SNARE诱导膜融合的分子机制。结果表明，当t - SNARE相关的脂质膜在Ca(2 +)存在的情况下与v - SNARE相关的囊泡接触时，SNARE蛋白以环状排列相互作用形成传导通道，从而在相对的双层膜之间建立连续性。进一步证明，SNARE使相对的双层膜靠近至2 - 3埃的距离，使Ca(2 +)能够连接它们。Ca(2 +)对双层膜的连接随后导致在接触部位双层膜之间的水被排出，从而实现脂质混合和膜融合。相对双层膜的钙桥接导致水的释放，这既来自水合Ca(2 +)离子的水壳，也来自脂质膜中磷酸头部基团处松散配位的水的置换。这些发现首次揭示了细胞中SNARE诱导膜融合的分子机制。本综述简要讨论了一些具有开创性的发现。
