Novel Insights into V-ATPase Functioning: Distinct Roles for its Accessory Subunits ATP6AP1/Ac45 and ATP6AP2/(pro) Renin Receptor

Author(s): Eric J.R. Jansen, Gerard J.M. Martens.

Journal Name: Current Protein & Peptide Science

Volume 13 , Issue 2 , 2012

Abstract:

The vacuolar (H+)-ATPase (V-ATPase) is a universal proton pump and its activity is required for a variety of cell-biological processes such as membrane trafficking, receptor-mediated endocytosis, lysosomal protein degradation, osteoclastic bone resorption and maintenance of acid-base homeostasis by renal intercalated cells. In neuronal and neuroendocrine cells, the V-ATPase is the major regulator of intragranular acidification which is indispensable for correct prohormone processing and neurotransmitter uptake. In these specialized cells, the V-ATPase is equipped with the accessory subunits ATP6AP1/Ac45 and ATP6AP2/(pro) renin receptor. Recent studies have shown that Ac45 interacts with the V0- sector of the V-ATPase complex, thereby regulating the intragranular pH and Ca2+-dependent exocytotic membrane fusion. Thus, Ac45 can be considered as a V-ATPase regulator in the neuroendocrine secretory pathway. ATP6AP2 has recently been found to be identical to the (pro) renin receptor and has a dual role: (i) in the renin-angiotensin system that also regulates V-ATPase activity; (ii) acting as an adapter by binding to both the V-ATPase and the Wnt receptor complex, thereby recruiting the receptor complex into an acidic microenvironment. We here provide an overview of the two V-ATPase accessory subunits as novel key players in V-ATPase regulation. We argue that the accessory subunits are candidate genes for V-ATPase-related human disorders and promising targets for manipulating V-ATPase functioning in vivo.

Keywords: Acidification, secretory pathway, membrane fusion, neurodevelopment, osteoporosis, renin-angiotensin system, endocytosis, teoclasts, eurotransmitter transporters, F-ATPase complex

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Article Details

VOLUME: 13
ISSUE: 2
Year: 2012
Page: [124 - 133]
Pages: 10
DOI: 10.2174/138920312800493160
Price: $58

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