Did2 coordinates Vps4-mediated dissociation of ESCRT-III from endosomes.
Did2 coordinates Vps4-mediated dissociation of ESCRT-III from endosomes.
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DOI：
10.1083/jcb.200606113
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发表时间：
2006-12-04
期刊：
影响因子：
--
通讯作者：
Odorizzi G
中科院分区：
文献类型：
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作者：
Nickerson DP;West M;Odorizzi G
将跨膜货物蛋白分选到多泡体（MVB）的内腔囊泡中取决于将转运所需的内体分选复合物（ESCRT）募集到内体膜的胞质面。ESCRT复合物从内体的随后解离需要Vps 4，其为腺苷三磷酸酶的AAA家族的成员。我们发现，Did 2指导Vps 4活性的ESCRT-III的解离，但没有作用的ESCRT-I或-II的解离。令人惊讶的是，囊泡出芽进入内体腔在Did 2功能不存在的情况下发生，即使Did 2是将MVB货物蛋白有效分选到内腔囊泡中所需的。MVB货物分选和内腔囊泡形成的这种解偶联表明，Vps 4介导的ESCRT-III解离是将货物蛋白分选到MVB囊泡中的必要步骤，但不是囊泡出芽到内体内腔中的先决条件。
The sorting of transmembrane cargo proteins into the lumenal vesicles of multivesicular bodies (MVBs) depends on the recruitment of endosomal sorting complexes required for transport (ESCRTs) to the cytosolic face of endosomal membranes. The subsequent dissociation of ESCRT complexes from endosomes requires Vps4, a member of the AAA family of adenosine triphosphatases. We show that Did2 directs Vps4 activity to the dissociation of ESCRT-III but has no role in the dissociation of ESCRT-I or -II. Surprisingly, vesicle budding into the endosome lumen occurs in the absence of Did2 function even though Did2 is required for the efficient sorting of MVB cargo proteins into lumenal vesicles. This uncoupling of MVB cargo sorting and lumenal vesicle formation suggests that the Vps4-mediated dissociation of ESCRT-III is an essential step in the sorting of cargo proteins into MVB vesicles but is not a prerequisite for the budding of vesicles into the endosome lumen.