title: The osteoclast and its unique cytoskeleton.
abstract: The osteoclast cytoskeleton is a unique structure that polarizes the cell's resorptive machinery to the bone-cell interface where it creates an isolated resorptive microenvironment consisting of an actin ring surrounding a ruffled border. This polarization process occurs under the aegis of the α(v) β(3)  integrin in collaboration with the M-CSF receptor, c-Fms. When occupied, α(v) β(3)  activates a canonical signaling complex consisting of c-Src, Syk, Dap12, Slp76, Vav 3, and Rac that permits the cell to spread and form actin rings. Generation of the ruffled border, the cell's resorptive organelle, is an exocytic process wherein synaptotagmin VII mediates fusion of secretory lysosomes to the bone-apposed plasma membrane. Absence of any component of this signaling pathway compromises osteoclast cytoskeletal organization and abridges bone resorption.
authors.affiliation: Departments of Pathology and Immunology, and Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. teitelbs@wustl.edu
authors.forename: Steven L
authors.initials: SL
authors.lastname: Teitelbaum
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D000081247:CSK Tyrosine-Protein Kinase; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009928:Organ Specificity / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000072377:Syk Kinase; D050857:Synaptotagmins / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D019061:src-Family Kinases
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D039302:Integrin alphaVbeta3; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D051567:Proto-Oncogene Proteins c-vav; C092947:SLP-76 signal Transducing adaptor proteins; C494302:SYT7 protein, human; C110546:TYROBP protein, human; C496621:VAV3 protein, human; D050857:Synaptotagmins; D011505:Protein-Tyrosine Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor; D000081247:CSK Tyrosine-Protein Kinase; C000606896:SYK protein, human; D000072377:Syk Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D020744:rac GTP-Binding Proteins