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NO-dependent osteoclast motility: reliance on cGMP-dependent protein kinase I and VASP
- Source :
- Journal of Cell Science. 118:5479-5487
- Publication Year :
- 2005
- Publisher :
- The Company of Biologists, 2005.
-
Abstract
- The osteoclast degrades bone in cycles; between cycles, the cell is motile. Resorption occurs by acid transport into an extracellular compartment defined by an alphavbeta3 integrin ring. NO has been implicated in the regulation of bone turnover due to stretch or via estrogen signals, but a specific mechanism linking NO to osteoclastic activity has not been described. NO stimulates osteoclast motility, and at high concentrations NO causes detachment and terminates resorption. Here we demonstrate that NO regulates attachment through the cGMP-dependent protein kinase I (PKG I) via phosphorylation of the intermediate protein VASP. VASP colocalized with the alphavbeta3 ring in stationary cells, but alternating bands of VASP and alphavbeta3 occurred when motility was induced by NO donors or cGMP. Redistribution of VASP correlated with its phosphorylation. Dependency of NO-induced motility on PKG I and on VASP was shown by siRNA knockdown of each protein. VASP knockdown also altered distribution of alphavbeta3 at the attachment site. We conclude that PKG I and VASP are essential for reorganization of attachment and cytoplasmic proteins in motility induced by NO or by cGMP.
- Subjects :
- Integrin
Osteoclasts
Motility
macromolecular substances
Biology
Nitric Oxide
Cell Movement
Osteoclast
Cyclic GMP-Dependent Protein Kinases
medicine
Extracellular
Humans
Nitric Oxide Donors
Phosphorylation
Protein kinase A
Cyclic GMP
Cells, Cultured
Cyclic GMP-Dependent Protein Kinase Type I
Gene knockdown
Microfilament Proteins
Vasodilator-stimulated phosphoprotein
Cell Biology
Integrin alphaVbeta3
Phosphoproteins
Cell biology
medicine.anatomical_structure
biology.protein
Cell Adhesion Molecules
Subjects
Details
- ISSN :
- 14779137 and 00219533
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Science
- Accession number :
- edsair.doi.dedup.....d4f9dbabb1863cce620cfd9a9cbd7a32