NO-dependent osteoclast motility: reliance on cGMP-dependent protein kinase I and VASP
Author:
Yaroslavskiy Beatrice B.1, Zhang Yongjun1, Kalla Sara E.1, Palacios Verónica García1, Sharrow Allison C.1, Li Yanan1, Zaidi Mone2, Wu Chuanyue1, Blair Harry C.1
Affiliation:
1. Departments of Pathology and of Cell Biology and Physiology, University of Pittsburgh and Veteran's Affairs Medical Center, Pittsburgh, PA 15243, USA 2. Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
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 αvβ3 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 αvβ3 ring in stationary cells, but alternating bands of VASP and αvβ3 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 αvβ3 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.
Publisher
The Company of Biologists
Reference39 articles.
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