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Authors: Reinhard Dechant and Matthias Peter

Reinhard Dechant

Corresponding author: reinhard.dechant@bc.biol.ethz.ch
Institute of Biochemistry; ETH Zurich; Zurich, Switzerland

Matthias Peter

Corresponding author: matthias.peter@bc.biol.ethz.ch
Institute of Biochemistry; Department of Biology; ETH Zürich; Zürich, Switzerland

Regulation of the activity of vacuolar ATPase (V-ATPase) is a well known, yet poorly understood phenomenon, which might underlie the contribution of V-ATPases in various cellular signaling processes1. In yeast, V-ATPase is regulated by glucose and contributes to activation of cAMP-dependent protein kinase A (PKA). We have recently shown that, in vivo, glucose regulates V-ATPase through cytosolic pH, suggesting that V-ATPase contains a pH sensitive subunit, which regulates assembly of the holo-complex2. Here, we present the purification and biochemical characterization of the N-terminal domain of subunit 'a', Vph1N, which has been suggested to act as a pH sensor in mammalian cells3. Interestingly, our studies demonstrate pH-dependent oligomerization of this domain in vivo and in vitro. Moreover, we identify a membrane proximal region that is required for the pH-dependent oligomerization, and suggest a speculative model for the regulation of the V-ATPase holo-complex by pH.

Article Addendum to:
R Dechant, M Binda, SS Lee, S Pelet, J Winderickx, M Peter. Cytosolic pH is a second messenger for glucose and regulates the PKA pathway through V-ATPase. EMBO J 2010; 29: 2515-26
PMID: 20562827 DOI: 10.1038/emboj.2010.1