title: Critical role of cortactin in actin ring formation and osteoclastic bone resorption.
abstract: Tyrosine kinase c-Src plays an essential role in ruffled border formation and bone resorption in osteoclasts; however, it is unclear how c-Src controls ruffled border formation during bone resorption. To address this question, we investigated the role of cortactin, a c-Src substrate, in osteoclasts. We found that cortactin showed colocalization with c-Src and actin rings in osteoclasts. Overexpression of cortactin stimulated actin ring formation in RAW 264.7 cells. In contrast, overexpression of Csk inhibited tyrosine phosphorylation of cortactin and binding of cortactin to c-Src. More importantly, overexertion of a mutant cortactin strongly suppressed actin ring formation and bone resorbing activity in osteoclasts. Collectively, our data indicate that cortactin controls osteoclastic bone resorption by regulating actin organization.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, 565-0871, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Matsubara
authors.forename: Akira
authors.initials: A
authors.lastname: Myoui
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Ikeda
authors.forename: Kenji
authors.initials: K
authors.lastname: Hata
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Riko
authors.initials: R
authors.lastname: Nishimura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002460:Cell Line; D051356:Cortactin / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology
chemical_list: D000199:Actins; D051356:Cortactin; D016392:Proto-Oncogene Proteins pp60(c-src)