Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13
Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13
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DOI：
10.1016/s0092-8674(00)81966-2
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发表时间：
1999-08-06
期刊：
影响因子：
64.5
通讯作者：
Zerial, M
中科院分区：
文献类型：
--
作者：
McBride, HM;Rybin, V;Zerial, M
SNARE和Rab GTP酶通过一种尚不清楚的机制在囊泡运输中合作。我们现在证明Rab 5效应子EEA 1和Rabaptin-5/Rabex-5以高分子量低聚物的形式存在于膜上，这些低聚物也含有NSF。寡聚体组装受NSF的ATP酶活性调节。突触融合蛋白13是内体融合所需的t-SNARE，通过与EEA 1的直接相互作用瞬时掺入大寡聚体中。这种相互作用是驱动融合所必需的，因为显性负性EEA 1和编码MIE Zn 2+指的合成肽都阻碍相互作用并阻断融合。我们提出了一种新的机制，即寡聚EEA 1和NSF介导的局部激活syntaxin 13膜拴系，并通过类比与病毒融合蛋白，协调装配的融合孔。
SNAREs and Rab GTPases cooperate in vesicle transport through a mechanism yet poorly understood. We now demonstrate that the Rab5 effecters EEA1 and Rabaptin-5/Rabex-5 exist on the membrane in high molecular weight oligomers, which also contain NSF. Oligomeric assembly is modulated by the ATPase activity of NSF. Syntaxin 13, the t-SNARE required for endosome fusion, is transiently incorporated into the large oligomers via direct interactions with EEA1. This interaction is required to drive fusion, since both dominant-negative EEA1 and synthetic peptides encoding the MIE Zn2+ finger hinder the interaction and block fusion. We propose a novel mechanism whereby oligomeric EEA1 and NSF mediate the local activation of syntaxin 13 upon membrane tethering and, by analogy with viral fusion proteins, coordinate the assembly of a fusion pore.