Cbl-PI3K interaction regulates Cathepsin K secretion in osteoclasts.

ABSTRACT: Effective bone resorption by osteoclasts is critical for balanced bone remodeling. We have previously reported that mice harboring a substitution mutation of tyrosine 737 to phenylalanine in the adapter protein Cbl (Cbl^Y737F, YF) have increased bone volume partly due to decreased osteoclast-mediated bone resorption. The Cbl^Y737F mutation abrogates interaction between Cbl and the p85 subunit of PI3K. Here, we studied the mechanism for defective resorptive function of YF mutant osteoclasts. The YF osteoclasts had intact actin cytoskeletons and sealing zones. Expression and localization of proteins needed for acidification of the resorptive lacunae were also comparable between the WT and YF osteoclasts. In contrast, secretion of Cathepsin K, a major protease needed to de

SUBMITTER: Yu J 

PROVIDER: S-EPMC6708784 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature