ArticleThe Journal of biological chemistry2013
The N termini of a-subunit isoforms are involved in signaling between vacuolar H+-ATPase (V-ATPase) and cytohesin-2.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 44 citations in OpenAlex.
- Targeting vacuolar ATPase in tobacco whitefly,Journal of biosciences · 2025Review
- The cytosolic N-terminal domain of V-ATPase a-subunits is a regulatory hub targeted by multiple signals.Frontiers in molecular biosciences · 2023Review
- V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid.Frontiers in molecular biosciences · 2023Article
- Detection and quantification of the vacuolar H+ATPase using the Legionella effector protein SidK.The Journal of cell biology · 2022Article
- The V-ATPaseInternational journal of molecular sciences · 2021Review
- Energetics and structure of alanine-rich α-helices via adaptive steered molecular dynamics.Biophysical journal · 2021Article
- Emerging links between endosomal pH and cancer.Cancer metastasis reviews · 2020Review
- Vacuolar HBiotarget · 2017Article
- Direct interaction of the Golgi V-ATPase a-subunit isoform with PI(4)P drives localization of Golgi V-ATPases in yeast.Molecular biology of the cell · 2017Article
- Mapping the H(+) (V)-ATPase interactome: identification of proteins involved in trafficking, folding, assembly and phosphorylation.Scientific reports · 2015Article
- Recent Insights into the Structure, Regulation, and Function of the V-ATPases.Trends in biochemical sciences · 2015Review
- The membrane domain of vacuolar H(+)ATPase: a crucial player in neurotransmitter exocytotic release.Cellular and molecular life sciences : CMLS · 2015Review
- Inhibition of Cytohesins Protects against Genetic Models of Motor Neuron Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Molecular mechanisms and regulation of urinary acidification.Comprehensive Physiology · 2014Review
- The V-ATPase membrane domain is a sensor of granular pH that controls the exocytotic machinery.The Journal of cell biology · 2013Article
- Regulation of luminal acidification by the V-ATPase.Physiology (Bethesda, Md.) · 2013Review
- Structural analysis of the N-terminal domain of subunit a of the yeast vacuolar ATPase (V-ATPase) using accessibility of single cysteine substitutions to chemical modification.The Journal of biological chemistry · 2013Article
- Crystal and NMR structures give insights into the role and dynamics of subunit F of the eukaryotic V-ATPase from Saccharomyces cerevisiae.The Journal of biological chemistry · 2013Article
- Allosteric properties of PH domains in Arf regulatory proteins.Cellular logisticsReview
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
Previously, we reported an acidification-dependent interaction of the endosomal vacuolar H(+)-ATPase (V-ATPase) with cytohesin-2, a GDP/GTP exchange factor (GEF), suggesting that it functions as a pH-sensing receptor. Here, we have studied the molecular mechanism of signaling between the V-ATPase, cytohesin-2, and Arf GTP-binding proteins. We found that part of the N-terminal cytosolic tail of the V-ATPase a2-subunit (a2N), corresponding to its first 17 amino acids (a2N(1-17)), potently modulates the enzymatic GDP/GTP exchange activity of cytohesin-2. Moreover, this peptide strongly inhibits GEF activity via direct interaction with the Sec7 domain of cytohesin-2. The structure of a2N(1-17) and its amino acids Phe(5), Met(10), and Gln(14) involved in interaction with Sec7 domain were determined by NMR spectroscopy analysis. In silico docking experiments revealed that part of the V-ATPase formed by its a2N(1-17) epitope competes with the switch 2 region of Arf1 and Arf6 for binding to the Sec7 domain of cytohesin-2. The amino acid sequence alignment and GEF activity studies also uncovered the conserved character of signaling between all four (a1-a4) a-subunit isoforms of mammalian V-ATPase and cytohesin-2. Moreover, the conserved character of this phenomenon was also confirmed in experiments showing binding of mammalian cytohesin-2 to the intact yeast V-ATPase holo-complex. Thus, here we have uncovered an evolutionarily conserved function of the V-ATPase as a novel cytohesin-signaling receptor.
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