Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics
Varp is a Rab21 guanine nucleotide exchange factor and regulates endosome dynamics
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DOI：
10.1242/jcs.02810
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发表时间：
2006-03-15
影响因子：
4
通讯作者：
Chang, ZJ
中科院分区：
文献类型：
--
作者：
Zhang, XJ;He, X;Chang, ZJ
小分子GTP酶Rab5和Rab21关系密切，在细胞内转运过程中发挥重要作用。Rab5受含有VPS9结构域的鸟嘌呤核苷酸交换因子的调控。在这里，我们描述了一种新的带有Ankyrin重复序列的VPS9结构域蛋白，即VPS9-ankyrin-Repeat蛋白(VARP)。VARP优先与GDP结合的Rab21相互作用，并且与Rab21的鸟核苷酸交换活性比Rab5强得多。此外，RNAi介导的内源性Varp缺失显著干扰HeLa细胞中Rab21的活性。异位表达的Varp主要定位于早期内小体，并导致早期内小体增大和巨大的晚期内小体。VPS9结构域和Ankyrin重复序列都是VARP在体内定位和活性所必需的。这些结果表明，VARP是一种潜在的Rab21鸟嘌呤核苷酸交换因子，可能调节体内的内体动力学。
The small GTPases Rab5 and Rab21 are closely related, and play essential roles in endocytic trafficking. Rab5 is regulated by VPS9-domain-containing guanine nucleotide exchange factors. Here, we describe a new VPS9-domain protein with ankyrin repeats, the VPS9-ankyrin-repeat protein (Varp). Varp interacts preferentially with GDP-bound Rab21 and has a much stronger guanine nucleotide exchange activity towards Rab21 than Rab5. Furthermore, RNAi-mediated depletion of endogenous Varp significantly disrupts the activity of Rab21 in HeLa cells. Ectopically expressed Varp mainly localizes to early endosomes and causes enlargement of early endosomes and giant late endosomes. Both the VPS9 domain and ankyrin-repeats are required for the endosomal localization and the activity of Varp in vivo. These results suggest that Varp is a potential Rab21 guanine nucleotide exchange factor and might regulate endosome dynamics in vivo.