title: Recent Insights into the Structure, Regulation, and Function of the V-ATPases.
abstract: The vacuolar (H(+))-ATPases (V-ATPases) are ATP-dependent proton pumps that acidify intracellular compartments and are also present at the plasma membrane. They function in such processes as membrane traffic, protein degradation, virus and toxin entry, bone resorption, pH homeostasis, and tumor cell invasion. V-ATPases are large multisubunit complexes, composed of an ATP-hydrolytic domain (V1) and a proton translocation domain (V0), and operate by a rotary mechanism. This review focuses on recent insights into their structure and mechanism, the mechanisms that regulate V-ATPase activity (particularly regulated assembly and trafficking), and the role of V-ATPases in processes such as cell signaling and cancer. These developments have highlighted the potential of V-ATPases as a therapeutic target in a variety of human diseases.
authors.affiliation: Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Cotter
authors.affiliation: Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Stransky
authors.affiliation: Program in Biochemistry, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: McGuire
authors.affiliation: Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA; Program in Biochemistry, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA; Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. Electronic address: michael.forgac@tufts.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Forgac
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D006180:Proton-Translocating ATPases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D006180:Proton-Translocating ATPases
keywords: V-ATPase; acidification; cancer; cell signaling; membrane traffic; proton transport