A new V-ATPase regulatory mechanism mediated by the Rab interacting lysosomal protein (RILP).
A new V-ATPase regulatory mechanism mediated by the Rab interacting lysosomal protein (RILP).
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DOI：
10.4161/cib.29616
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发表时间：
2014-10
影响因子：
--
通讯作者：
Bucci C
中科院分区：
文献类型：
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作者：
De Luca M;Bucci C
细胞内腔室的渐进式腔内酸化对其功能至关重要。质子进入细胞器管腔的转运是由液泡atp酶（v - atp酶）介导的，大型多亚基质子泵被组织成2个结构域，V0和V1，一起作为一个旋转机器工作。每个亚基与特定伙伴的相互作用在控制V-ATPase活性中起着至关重要的作用。最近，我们已经证明RILP是一种调节多泡体（MVBs）后期内噬运输和生物发生的Rab7效应物，是V-ATPase亚基V1G1的特异性相互作用物，V1G1是外周茎正确组装V-ATPase的基本成分。RILP在核内体和溶酶体水平上控制V1G1的稳定性和定位，影响v - atp酶的组装和功能。这一新的v - atp酶调控机制的发现为理解细胞器的pH调节开辟了新的思路，揭示了RILP在控制内核体向溶酶体转运的不同方面的关键作用。
Progressive luminal acidification of intracellular compartments is important for their functions. Proton transport into the organelle's lumen is mediated by vacuolar ATPases (V-ATPases) large multi-subunit proton pumps organized into 2 domains, V0 and V1, working together as a rotary machine. The interaction of each subunit with specific partners plays a crucial role in controlling V-ATPase activity. Recently, we have shown that RILP, a Rab7 effector regulating late endocytic traffic and biogenesis of multivesicular bodies (MVBs), is a specific interactor of the V-ATPase subunit V1G1, a fundamental component of the peripheral stalk for correct V-ATPase assembly. RILP controls V1G1 stability and localization affecting V-ATPase assembly and function at the level of endosomes and lysosomes. The discovery of this new regulatory mechanism for V-ATPase opens new scenario to the comprehension of organelle's pH regulation and reveals a key role of RILP in controlling different aspects of endosome to lysosome transport.