V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway
V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway
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DOI：
10.1038/ncb1348
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发表时间：
2006-02-01
影响因子：
21.3
通讯作者：
Marshansky, V
中科院分区：
文献类型：
--
作者：
Hurtado-Lorenzo, A;Skinner, M;Marshansky, V
小GTd 6 Arf 6和ARNO从胞质溶胶到内体膜的募集由V-ATP酶依赖性内体酸化驱动。介导这种pH敏感性募集的分子机制及其作用尚不清楚。在这里，我们证明了Arf 6与C-亚基相互作用，ARNO与V-ATPase的α 2-同种型相互作用。α 2-同种型靶向早期内体，以内体内酸化依赖性方式与ARNO相互作用，并且这种相互作用的破坏导致内吞作用的可逆抑制。内体酸化的抑制消除了早期和晚期内体区室之间的蛋白质运输。这些数据证明了早期内体酸化和V-ATP酶/ARNO/Arf 6相互作用在内吞降解途径的调节中的关键作用。他们还表明，V-ATP酶可以通过募集和与ARNO和Arf 6相互作用来调节膜运输;这些特征与V-ATP酶作为内体pH传感机制的重要组成部分的作用一致。
The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. They also indicate that V-ATPase could modulate membrane trafficking by recruiting and interacting with ARNO and Arf6; characteristics that are consistent with the role of V-ATPase as an essential component of the endosomal pH-sensing machinery.