title: Interactions between vacuolar H+-ATPases and microfilaments in osteoclasts.
abstract: Vacuolar H(+)-ATPases (V-ATPases) are transported from cytosolic compartments to the ruffled plasma membrane of osteoclasts as they activate to resorb bone. Transport of V-ATPases is essential for bone resorption, and is associated with binding interactions between V-ATPases and microfilaments that are mediated by an actin-binding site in subunit B. This site is contained within 44 amino acids in the amino terminal domain, and requires a sequence motif that resembles an actin-binding motif found in mammalian profilin 1. Small alterations in the profilin-like sequence disrupt the actin-binding activity of subunit B. The interaction between V-ATPases and microfilaments in osteoclasts is regulated in response to changes in phosphatidylinositol-3 kinase activity. During internalization of V-ATPases from the plasma membrane of osteoclasts after a cycle of resorption, V-ATPases bind microfilaments that are in podosomes, dynamic actin-based structures, also present in metastatic cancer cells. Studies are ongoing to establish the physiological role of the microfilament-binding activity of subunit B in osteoclasts and in other cells.
authors.affiliation: Department of Orthodontics, University of Florida College of Dentistry, Gainesville, Florida, USA. sholliday@dental.ufl.edu
authors.forename: L Shannon
authors.initials: LS
authors.lastname: Holliday
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bubb
authors.forename: Jin
authors.initials: J
authors.lastname: Jiang
authors.forename: I Rita
authors.initials: IR
authors.lastname: Hurst
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D008840:Microfilament Proteins; D010010:Osteoclasts / Q000737:chemistry / Q000201:enzymology*; D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases