RILP regulates vacuolar ATPase through interaction with the V1G1 subunit
RILP regulates vacuolar ATPase through interaction with the V1G1 subunit
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DOI：
10.1242/jcs.142604
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发表时间：
2014-06-15
影响因子：
4
通讯作者：
Bucci, Cecilia
中科院分区：
文献类型：
--
作者：
De Luca, Maria;Cogli, Laura;Bucci, Cecilia
Rab-interacting lysosomal protein（RILP）是Rab 7 GTP酶的下游效应子。GTP结合的Rab 7将RILP募集到内体膜，并且它们一起控制晚期内吞运输、吞噬体和自噬体成熟，并且负责信号传导受体降解。我们已经确定，使用不同的方法，V1 G1（正式称为ATP 6V 1G 1）的液泡ATP酶（V-ATP酶）的亚基作为RILP相互作用蛋白。V1 G1是外周柄的一个组成部分，是正确的V-ATP酶组装的基础。我们在这里表明，RILP调节招聘V1 G1晚期内体和溶酶体膜，但也控制V1 G1的稳定性。事实上，我们证明，V1 G1可以被泛素化，RILP是负责V1 G1的蛋白酶体降解。此外，我们证明V1 G1表达水平的改变损害V-ATP酶活性。因此，我们的数据首次表明RILP通过与V1 G1的相互作用调节V-ATP酶的活性。鉴于V-ATP酶在几种细胞过程和人类疾病中的重要性，这些数据表明RILP活性的调节可用于控制V-ATP酶功能。
Rab-interacting lysosomal protein (RILP) is a downstream effector of the Rab7 GTPase. GTP-bound Rab7 recruits RILP to endosomal membranes and, together, they control late endocytic traffic, phagosome and autophagosome maturation and are responsible for signaling receptor degradation. We have identified, using different approaches, the V1G1 (officially known as ATP6V1G1) subunit of the vacuolar ATPase (V-ATPase) as a RILP-interacting protein. V1G1 is a component of the peripheral stalk and is fundamental for correct V-ATPase assembly. We show here that RILP regulates the recruitment of V1G1 to late endosomal and lysosomal membranes but also controls V1G1 stability. Indeed, we demonstrate that V1G1 can be ubiquitylated and that RILP is responsible for proteasomal degradation of V1G1. Furthermore, we demonstrate that alterations in V1G1 expression levels impair V-ATPase activity. Thus, our data demonstrate for the first time that RILP regulates the activity of the V-ATPase through its interaction with V1G1. Given the importance of V-ATPase in several cellular processes and human diseases, these data suggest that modulation of RILP activity could be used to control V-ATPase function.