Constitutively active ESCRT-II suppresses the MVB-sorting phenotype of ESCRT-0 and ESCRT-I mutants.
Constitutively active ESCRT-II suppresses the MVB-sorting phenotype of ESCRT-0 and ESCRT-I mutants.
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组成型活性ESCRT-II抑制ESCRT-0和ESCRT-I突变体的MVB分类表型。
DOI：
10.1091/mbc.e14-10-1469
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发表时间：
2015-02-01
影响因子：
3.3
通讯作者：
Babst M
中科院分区：
文献类型：
--
作者：
Mageswaran SK;Johnson NK;Odorizzi G;Babst M
这项研究朝着了解 MVB 生物发生和该过程中 ESCRT 机械的最低要求迈出了一步。早期的 ESCRT 复合体（ESCRT-0 和 -I）似乎在货物分拣方面具有冗余功能。此外，除了后期的 ESRT 机械之外，囊泡的形成似乎还需要货物分类。运输所需的内体分选复合物 (ESCRT) 蛋白复合物在内体上发挥作用，形成含有运往液泡/溶酶体腔的货物蛋白的腔内囊泡 (ILV)。早期的 ESCRT（ESCRT-0 和 -I）可能参与货物分拣，而 ESCRT-III 和 Vps4 的功能是切断正在形成的 ILV 的颈部。 ESCRT-II 通过以 ESCRT-I 调节的方式启动 ESCRT-III 形成来连接这些功能。我们鉴定了 ESCRT-II 的组成型活性突变体，该突变体部分抑制 ESCRT-I 或 ESCRT-0 缺失菌株的表型，表明这些早期 ESCRT 不是必需的并且具有冗余功能。然而，单独的 ESCRT-III/Vps4 系统不足以形成 ILV，还需要由早期 ESCRT 之一介导的货物分类。
This study is a step toward understanding the minimal requirements for MVB biogenesis and for ESCRT machinery in this process. Early ESCRT complexes (ESCRT-0 and -I) seem to have redundant functions in cargo sorting. Furthermore, vesicle formation seems to require cargo sorting in addition to late ESCRT machinery. The endosomal sorting complex required for transport (ESCRT) protein complexes function at the endosome in the formation of intraluminal vesicles (ILVs) containing cargo proteins destined for the vacuolar/lysosomal lumen. The early ESCRTs (ESCRT-0 and -I) are likely involved in cargo sorting, whereas ESCRT-III and Vps4 function to sever the neck of the forming ILVs. ESCRT-II links these functions by initiating ESCRT-III formation in an ESCRT-I–regulated manner. We identify a constitutively active mutant of ESCRT-II that partially suppresses the phenotype of an ESCRT-I or ESCRT-0 deletion strain, suggesting that these early ESCRTs are not essential and have redundant functions. However, the ESCRT-III/Vps4 system alone is not sufficient for ILV formation but requires cargo sorting mediated by one of the early ESCRTs.