Structural and functional understanding of disease-associated mutations in V-ATPase subunit a1 and other isoforms.

ABSTRACT: The vacuolar-type ATPase (V-ATPase) is a multisubunit protein composed of the cytosolic adenosine triphosphate (ATP) hydrolysis catalyzing V₁ complex, and the integral membrane complex, V_o, responsible for proton translocation. The largest subunit of the V_o complex, subunit a, enables proton translocation upon ATP hydrolysis, mediated by the cytosolic V₁ complex. Four known subunit a isoforms (a1-a4) are expressed in different cellular locations. Subunit a1 (also known as V_oa1), the neural isoform, is strongly expressed in neurons and is encoded by the ATP6V0A1 gene. Global knockout of this gene in mice causes embryonic lethality, whereas pyramidal neuron-specific knockout resulted in neuronal cell death with impaired spatial an

SUBMITTER: Indrawinata K 

PROVIDER: S-EPMC10352029 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature