ArticleThe Journal of biological chemistry2008
Cytoplasmic terminus of vacuolar type proton pump accessory subunit Ac45 is required for proper interaction with V(0) domain subunits and efficient osteoclastic bone resorption.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- ATP6AP1 promotes cell proliferation and tamoxifen resistance in luminal breast cancer by inducing autophagy.Cell death & disease · 2025Article
- ATP6AP2, a regulator of LRP6/β-catenin protein trafficking, promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner.Bone research · 2024Article
- Lysosomal biogenesis and function in osteoclasts: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
- Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association.Journal of inherited metabolic disease · 2023Article
- Ponicidin Treatment Improved the Cell Proliferation, Differentiation, and Calcium Mineralization on the Osteoblast-Like MG-63 Cells.Applied biochemistry and biotechnology · 2022Article
- The emerging role of furin in neurodegenerative and neuropsychiatric diseases.Translational neurodegeneration · 2022Review
- Regulation and function of V-ATPases in physiology and disease.Biochimica et biophysica acta. Biomembranes · 2020Review
- Sugary Logistics Gone Wrong: Membrane Trafficking and Congenital Disorders of Glycosylation.International journal of molecular sciences · 2020Review
- Effect of calcium glucoheptonate on proliferation and osteogenesis of osteoblast-like cells in vitro.PloS one · 2019Article
- NAFLD Phenotype in Patients With V-ATPase Proton Pump Assembly Defects.Cellular and molecular gastroenterology and hepatology · 2018Article
- Vacuolar HBiotarget · 2017Article
- Calmodulin interacts with Rab3D and modulates osteoclastic bone resorption.Scientific reports · 2016Article
- ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation.Nature communications · 2016Article
- Extracellular and Luminal pH Regulation by Vacuolar H+-ATPase Isoform Expression and Targeting to the Plasma Membrane and Endosomes.The Journal of biological chemistry · 2016Article
- Identification of domains within the V-ATPase accessory subunit Ac45 involved in V-ATPase transport and Ca2+-dependent exocytosis.The Journal of biological chemistry · 2012Article
- V-ATPase subunit ATP6AP1 (Ac45) regulates osteoclast differentiation, extracellular acidification, lysosomal trafficking, and protease exocytosis in osteoclast-mediated bone resorption.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2012Article
- Article
- VHA-19 is essential in Caenorhabditis elegans oocytes for embryogenesis and is involved in trafficking in oocytes.PloS one · 2012Article
- Tctex-1, a novel interaction partner of Rab3D, is required for osteoclastic bone resorption.Molecular and cellular biology · 2011Article
- Versatile roles of V-ATPases accessory subunit Ac45 in osteoclast formation and function.PloS one · 2011Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Solubilization of mineralized bone by osteoclasts is largely dependent on the acidification of the extracellular resorption lacuna driven by the vacuolar (H+)-ATPases (V-ATPases) polarized within the ruffled border membranes. V-ATPases consist of two functionally and structurally distinct domains, V(1) and V(0). The peripheral cytoplasmically oriented V(1) domain drives ATP hydrolysis, which necessitates the translocation of protons across the integral membrane bound V(0) domain. Here, we demonstrate that an accessory subunit, Ac45, interacts with the V(0) domain and contributes to the vacuolar type proton pump-mediated function in osteoclasts. Consistent with its role in intracellular acidification, Ac45 was found to be localized to the ruffled border region of polarized resorbing osteoclasts and enriched in pH-dependent endosomal compartments that polarized to the ruffled border region of actively resorbing osteoclasts. Interestingly, truncation of the 26-amino acid residue cytoplasmic tail of Ac45, which encodes an autonomous internalization signal, was found to impair bone resorption in vitro. Furthermore, biochemical analysis revealed that although both wild type Ac45 and mutant were capable of associating with subunits a3, c, c'', and d, deletion of the cytoplasmic tail altered its binding proximity with a3, c'', and d. In all, our data suggest that the cytoplasmic terminus of Ac45 contains elements necessary for its proper interaction with V(0) domain and efficient osteoclastic bone resorption.
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