In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 25, No. 8 ( 2014-04-15), p. 1251-1262
Abstract:
Vacuolar proton-translocating ATPases (V-ATPases) are highly conserved, ATP-driven proton pumps regulated by reversible dissociation of its cytosolic, peripheral V 1 domain from the integral membrane V o domain. Multiple stresses induce changes in V 1 -V o assembly, but the signaling mechanisms behind these changes are not understood. Here we show that certain stress-responsive changes in V-ATPase activity and assembly require the signaling lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P 2 ). V-ATPase activation through V 1 -V o assembly in response to salt stress is strongly dependent on PI(3,5)P 2 synthesis. Purified V o complexes preferentially bind to PI(3,5)P 2 on lipid arrays, suggesting direct binding between the lipid and the membrane sector of the V-ATPase. Increasing PI(3,5)P 2 levels in vivo recruits the N-terminal domain of V o -sector subunit Vph1p from cytosol to membranes, independent of other subunits. This Vph1p domain is critical for V 1 -V o interaction, suggesting that interaction of Vph1p with PI(3,5)P 2 -containing membranes stabilizes V 1 -V o assembly and thus increases V-ATPase activity. These results help explain the previously described vacuolar acidification defect in yeast fab1∆ and vac14∆ mutants and suggest that human disease phenotypes associated with PI(3,5)P 2 loss may arise from compromised V-ATPase stability and regulation.
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.e13-10-0563
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2014
detail.hit.zdb_id:
1474922-1
SSG:
12
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