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Testing the SNARE/SM protein model of membrane fusion

机译:测试膜融合的SNARE / SM蛋白模型

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摘要

In eukaryotic cells, the budding and fusion of membranes mediates diverse but essential processes, ranging from cell division to organelle biogenesis to neurotransmitter secretion. All intracellular membrane fusion except for mitochondrial fusion is driven by SNARE and SM (Secl/Muncl8-like) proteins (1-3). Membrane fusion has been particularly intensely studied for neurotransmitter secretion. In neurotransmitter secretion, fusion is mediated by the plasma membrane SNARE proteins syntaxin and syn-aptosomal-associated protein 25 (SNAP-25), the vesicle SNARE protein synapto-brevin/vesicle-associated membrane protein (VAMP), and the SM protein Muncl8-1 (Fig. 1 A and B). Mechanistically, SNARE proteins are thought to fuel fusion by forming a transcomplex between the vesicle and target membranes; in this complex, progressive zippering of a four-helical bundle formed by the SNARE motifs of SNARE proteins forces the fusing phospholipid membranes into close proximity, thereby destabilizing their surfaces (1-3). SM proteins are essential coagonists of SNARE proteins in fusion in that all intracellular SNARE-dependent fusion reactions require an SM protein.
机译:在真核细胞中,膜的出芽和融合介导了多种但必不可少的过程,从细胞分裂到细胞器生物发生再到神经递质分泌。除线粒体融合外,所有细胞内膜融合均由SNARE和SM(Secl / Munc18样)蛋白驱动(1-3)。对于神经递质的分泌,对膜融合的研究特别深入。在神经递质的分泌中,融合是由质膜SNARE蛋白syntaxin和同核小体相关蛋白25(SNAP-25),囊泡SNARE蛋白突触-brevin /囊泡相关膜蛋白(VAMP)和SM蛋白Muncl8介导的。 -1(图1 A和B)。从机理上讲,SNARE蛋白被认为通过在囊泡和靶膜之间形成一个复合物来促进融合。在这种复杂的情况下,由SNARE蛋白质的SNARE基序形成的四螺旋束的逐渐拉链会迫使融合的磷脂膜紧密靠近,从而使它们的表面不稳定(1-3)。 SM蛋白是SNARE蛋白在融合过程中的重要辅酶,因为所有细胞内依赖SNARE的融合反应均需要SM蛋白。

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    Department of Molecular and Cellular Physiology , Stanford University, Stanford,CA 94305-5453;

    Department of Molecular and Cellular Physiology , Stanford University, Stanford,CA 94305-5453;

    Department of Molecular and Cellular Physiology , Stanford University, Stanford,CA 94305-5453,Howard Hughes Medical Institute, Stanford University, Stanford,CA 94305-5453;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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