Critical role of cortactin in actin ring formation and osteoclastic bone resorption.
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.
Matsubara
Takuma
T
Department of Molecular and Cellular Biochemistry, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, 565-0871, Japan.
Myoui
Akira
A
Ikeda
Fumiyo
F
Hata
Kenji
K
Yoshikawa
Hideki
H
Nishimura
Riko
R
Yoneda
Toshiyuki
T
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
D000199:Actins; D051356:Cortactin; D016392:Proto-Oncogene Proteins pp60(c-src)