Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2-/- mice

Hava Gil-Henn, Olivier Destaing, Natalie A. Sims, Kazuhiro Aoki, Neil Alles, Lynn Neff, Archana Sanjay, Angela Bruzzaniti, Pietro De Camilli, Roland Baron, Joseph Schlessinger

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function. Pyk2-null osteoclasts were unable to transform podosome clusters into a podosome belt at the cell periphery; instead of a sealing zone only small actin rings were formed, resulting in impaired bone resorption. Furthermore, in Pyk2-null osteoclasts, Rho activity was enhanced while microtubule acetylation and stability were significantly reduced. Rescue experiments by ectopic expression of wild-type or a variety of Pyk2 mutants in osteoclasts from Pyk2?/? mice have shown that the FAT domain of Pyk2 is essential for podosome belt and sealing zone formation as well as for bone resorption. These experiments underscore an important role of Pyk2 in microtubule-dependent podosome organization, bone resorption, and other osteoclast functions.

Original languageEnglish (US)
Pages (from-to)1053-1064
Number of pages12
JournalJournal of Cell Biology
Volume178
Issue number6
DOIs
StatePublished - Sep 10 2007
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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    Gil-Henn, H., Destaing, O., Sims, N. A., Aoki, K., Alles, N., Neff, L., Sanjay, A., Bruzzaniti, A., De Camilli, P., Baron, R., & Schlessinger, J. (2007). Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2-/- mice. Journal of Cell Biology, 178(6), 1053-1064. https://doi.org/10.1083/jcb.200701148