C-Src-mediated phosphorylation of thyroid hormone receptor-interacting protein 6 (TRIP6) promotes osteoclast sealing zone formation.

ABSTRACT: Osteoclasts resorb bone through the formation of a unique attachment structure called the sealing zone. In this study, a role for thyroid hormone receptor-interacting protein 6 (TRIP6) in sealing zone formation and osteoclast activity was examined. TRIP6 was shown to reside in the sealing zone through its association with tropomyosin 4, an actin-binding protein that regulates sealing dimensions and bone resorptive capacity. Suppression of TRIP6 in mature osteoclasts by RNA interference altered sealing zone dimensions and inhibited bone resorption, whereas overexpression of TRIP6 increased the sealing zone perimeter and enhanced bone resorption. Treatment of osteoclasts with lysophosphatidic acid (LPA), which phosphorylates TRIP6 at tyrosine 55 through a c-Src-dependent mechanism, caused in

SUBMITTER: McMichael BK 

PROVIDER: S-EPMC2924104 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature