biostudies-literatureEaton AFNIDDK NIH HHSInflammatory Bowel Disease CenterNational Institutes of HealthBoston Area Diabetes and Endocrinology Research CenterNIH HHSzqae025https://www.ebi.ac.uk/biostudies/studies/S-EPMC11237898biostudies-literatureUnknown5(4)The proton pumping V-ATPase drives essential biological processes, such as acidification of intracellular organelles. Critically, the V-ATPase domains, V1 and VO, must assemble to produce a functional holoenzyme. V-ATPase dysfunction results in cancer, neurodegeneration, and diabetes, as well as systemic acidosis caused by reduced activity of proton-secreting kidney intercalated cells (ICs). However, little is known about the molecular regulation of V-ATPase in mammals. We identified a novel interactor of the mammalian V-ATPase, Drosophila melanogaster X chromosomal gene-like 1 (Dmxl1), aka Rabconnectin-3A. The yeast homologue of Dmxl1, Rav1p, is part of a complex that catalyzes the reversible assembly of the domains. We, therefore,hypothesized that Dmxl1 is a mammalian V-ATPase assembly fFunction (Oxford, England)Dmxl1 Is an Essential Mammalian Gene that Is Required for V-ATPase Assembly and Function In Vivo.PMC11237898DK043351T32 DK007540P30 DK135043DK135043P30 DK043351R01 DK121848S10 OD021577OD021577Eaton AFDanielson ECMerkulova MBrown DCapen DfalseDmxl1 Is an Essential Mammalian Gene that Is Required for V-ATPase Assembly and Function In Vivo.The proton pumping V-ATPase drives essential biological processes, such as acidification of intracellular organelles. Critically, the V-ATPase domains, V1 and VO, must assemble to produce a functional holoenzyme. V-ATPase dysfunction results in cancer, neurodegeneration, and diabetes, as well as systemic acidosis caused by reduced activity of proton-secreting kidney intercalated cells (ICs). However, little is known about the molecular regulation of V-ATPase in mammals. We identified a novel interactor of the mammalian V-ATPase, Drosophila melanogaster X chromosomal gene-like 1 (Dmxl1), aka Rabconnectin-3A. The yeast homologue of Dmxl1, Rav1p, is part of a complex that catalyzes the reversible assembly of the domains. We, therefore,hypothesized that Dmxl1 is a mammalian V-ATPase assembly f2024-01-01T00:00:00Z2024 Jul2025-04-19T01:04:14.044Z2025-04-07T12:00:54.165ZS-EPMC112378983898498910.1093/function/zqae025