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

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 t...

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Autores principales: Gil-Henn, Hava, Destaing, Olivier, Sims, Natalie A., Aoki, Kazuhiro, Alles, Neil, Neff, Lynn, Sanjay, Archana, Bruzzaniti, Angela, De Camilli, Pietro, Baron, Roland, Schlessinger, Joseph
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064627/
https://www.ncbi.nlm.nih.gov/pubmed/17846174
http://dx.doi.org/10.1083/jcb.200701148
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author Gil-Henn, Hava
Destaing, Olivier
Sims, Natalie A.
Aoki, Kazuhiro
Alles, Neil
Neff, Lynn
Sanjay, Archana
Bruzzaniti, Angela
De Camilli, Pietro
Baron, Roland
Schlessinger, Joseph
author_facet Gil-Henn, Hava
Destaing, Olivier
Sims, Natalie A.
Aoki, Kazuhiro
Alles, Neil
Neff, Lynn
Sanjay, Archana
Bruzzaniti, Angela
De Camilli, Pietro
Baron, Roland
Schlessinger, Joseph
author_sort Gil-Henn, Hava
collection PubMed
description 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.
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spelling pubmed-20646272008-03-10 Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(−/−) mice Gil-Henn, Hava Destaing, Olivier Sims, Natalie A. Aoki, Kazuhiro Alles, Neil Neff, Lynn Sanjay, Archana Bruzzaniti, Angela De Camilli, Pietro Baron, Roland Schlessinger, Joseph J Cell Biol Research Articles 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. The Rockefeller University Press 2007-09-10 /pmc/articles/PMC2064627/ /pubmed/17846174 http://dx.doi.org/10.1083/jcb.200701148 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Gil-Henn, Hava
Destaing, Olivier
Sims, Natalie A.
Aoki, Kazuhiro
Alles, Neil
Neff, Lynn
Sanjay, Archana
Bruzzaniti, Angela
De Camilli, Pietro
Baron, Roland
Schlessinger, Joseph
Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(−/−) mice
title Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(−/−) mice
title_full Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(−/−) mice
title_fullStr Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(−/−) mice
title_full_unstemmed Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(−/−) mice
title_short Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(−/−) mice
title_sort defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in pyk2(−/−) mice
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064627/
https://www.ncbi.nlm.nih.gov/pubmed/17846174
http://dx.doi.org/10.1083/jcb.200701148
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