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 language | English (US) |
|---|---|
| Pages (from-to) | 1053-1064 |
| Number of pages | 12 |
| Journal | Journal of Cell Biology |
| Volume | 178 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 10 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
Cite this
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.
In: Journal of Cell Biology, Vol. 178, No. 6, 10.09.2007, p. 1053-1064.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2-/- mice
AU - Gil-Henn, Hava
AU - Destaing, Olivier
AU - Sims, Natalie A.
AU - Aoki, Kazuhiro
AU - Alles, Neil
AU - Neff, Lynn
AU - Sanjay, Archana
AU - Bruzzaniti, Angela
AU - De Camilli, Pietro
AU - Baron, Roland
AU - Schlessinger, Joseph
PY - 2007/9/10
Y1 - 2007/9/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34548845081&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548845081&partnerID=8YFLogxK
U2 - 10.1083/jcb.200701148
DO - 10.1083/jcb.200701148
M3 - Article
C2 - 17846174
AN - SCOPUS:34548845081
VL - 178
SP - 1053
EP - 1064
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -