Regulators of Vps4 ATPase activity at endosomes differentially influence the size and rate of formation of intralumenal vesicles.

Regulators of Vps4 ATPase activity at endosomes differentially influence the size and rate of formation of intralumenal vesicles.
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DOI:
10.1091/mbc.e09-09-0776
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发表时间:
2010-03-15
影响因子:
3.3
通讯作者:
Odorizzi G
Odorizzi G
中科院分区:
生物学3区
文献类型:
--
作者:
Nickerson DP;West M;Henry R;Odorizzi G

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ESCRT-III 的分解需要调节蛋白控制下的 Vps4 ATPase 活性。这里描述的是 Vps4 调节剂的独特时空功能,其中 Did2 在调节 MVB 腔囊泡大小方面发挥独特的作用,Vtal-Vps60 促进有效的膜分裂和囊泡递送到内涵体腔中。将运输所需的内体分选复合物 (ESCRT) 募集到内体的胞质表面,调节跨膜蛋白选择性包含到多囊泡体 (MVB) 的腔囊泡中。 ESCRT-0、-I 和 -II 直接与 MVB 途径的泛素化跨膜货物结合,而 ESCRT-III 在内体上的聚合被认为会使膜弯曲和/或提供驱动膜分裂和囊泡脱离进入内体腔的能量。 ESCRT-III 聚合物的分解及其亚基与内体的解离需要 Vps4 ATP 酶,其活性在体内由调节蛋白控制。我们通过检查亚细胞定位和内体形态来确定 Vps4 调节蛋白的不同时空作用。 Did2 在调节 MVB 腔囊泡大小方面发挥着独特的作用,而 Vtal 和 Vps60 则促进有效的膜分裂和膜向内体腔的递送。这些形态学效应可能是由 Vps4 介导的 ESCRT-III 操作引起的,因为我们表明 ESCRT-0、-I 和 -II 从内体解离并不直接依赖于 Vps4 活性。
Disassembly of ESCRT-III requires Vps4 ATPase activity under the control of regulatory proteins. Described here are distinct spatiotemporal functions for Vps4 regulators, with Did2 playing a unique role in regulating MVB lumenal vesicle size and Vtal-Vps60 promoting efficient membrane scission and delivery of vesicles into the endosome lumen. Recruitment of endosomal sorting complexes required for transport (ESCRTs) to the cytosolic face of endosomes regulates selective inclusion of transmembrane proteins into the lumenal vesicles of multivesicular bodies (MVBs). ESCRT-0, -I, and -II bind directly to ubiquitinated transmembrane cargoes of the MVB pathway, whereas polymerization of ESCRT-III at endosomes is thought to bend the membrane and/or provide the energetic force that drives membrane scission and detachment of vesicles into the endosome lumen. Disassembly of the ESCRT-III polymer and dissociation of its subunits from endosomes requires the Vps4 ATPase, the activity of which is controlled in vivo by regulatory proteins. We identify distinct spatiotemporal roles for Vps4-regulating proteins through examinations of subcellular localization and endosome morphology. Did2 plays a unique role in the regulation of MVB lumenal vesicle size, whereas Vtal and Vps60 promote efficient membrane scission and delivery of membrane to the endosome lumen. These morphological effects probably result from Vps4-mediated manipulations of ESCRT-III, because we show dissociation of ESCRT-0, -I, and -II from endosomes is not directly dependent on Vps4 activity.
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