FHIP and FTS proteins are critical for dynein-mediated transport of early endosomes in Aspergillus
FHIP and FTS proteins are critical for dynein-mediated transport of early endosomes in Aspergillus
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DOI：
10.1091/mbc.e14-04-0873
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发表时间：
2014-07-15
影响因子：
3.3
通讯作者：
Xiang, Xin
中科院分区：
文献类型：
--
作者：
Yao, Xuanli;Wang, Xiangfeng;Xiang, Xin
负端定向微管运动细胞质动力蛋白运输各种细胞货物，包括早期核内体，但动力蛋白如何与其货物结合尚不清楚。最近发现真菌Hook同源物将动力蛋白与早期核内体的运输联系起来。本研究通过对早期核内体分布缺陷突变体的全基因组筛选，确定了nidulans中的FhipA是HookA （a . nidulans Hook）功能的关键参与者。FhipA的人类同源物FHIP是先前发现的FTS/Hook/FHIP （FHF）复合体中的一种蛋白质，该复合体除了含有FHIP和Hook蛋白外，还含有融合趾（FTS）。虽然该复合物先前未被证明参与动力蛋白介导的运输，但我们在这里表明，FhipA或FtsA （A. nidulans FTS同源物）的缺失会破坏hooka -早期内体关联并抑制早期内体运动。FhipA和FtsA都与早期核内体相关，有趣的是，FtsA-早期核内体关联需要FhipA和HookA，而FhipA-早期核内体关联独立于HookA和FtsA。因此，与HookA和FtsA相比，FhipA与早期核内体的联系更为直接。而在没有HookA或FtsA的情况下，FhipA蛋白水平明显降低。我们的研究结果表明，FtsA/HookA/FhipA复合体中的所有三种蛋白对动力蛋白介导的早期内体运动都很重要。
The minus end-directed microtubule motor cytoplasmic dynein transports various cellular cargoes, including early endosomes, but how dynein binds to its cargo remains unclear. Recently fungal Hook homologues were found to link dynein to early endosomes for their transport. Here we identified FhipA in Aspergillus nidulans as a key player for HookA (A. nidulans Hook) function via a genome-wide screen for mutants defective in earlyendosome distribution. The human homologue of FhipA, FHIP, is a protein in the previously discovered FTS/Hook/FHIP (FHF) complex, which contains, besides FHIP and Hook proteins, Fused Toes (FTS). Although this complex was not previously shown to be involved in dynein-mediated transport, we show here that loss of either FhipA or FtsA (A. nidulans FTS homologue) disrupts HookA-early endosome association and inhibits early endosome movement. Both FhipA and FtsA associate with early endosomes, and interestingly, while FtsA-early endosome association requires FhipA and HookA, FhipA-early endosome association is independent of HookA and FtsA. Thus FhipA is more directly linked to early endosomes than HookA and FtsA. However, in the absence of HookA or FtsA, FhipA protein level is significantly reduced. Our results indicate that all three proteins in the FtsA/HookA/FhipA complex are important for dynein-mediated early endosome movement.