Journal
JOURNAL OF CELL BIOLOGY
Volume 160, Issue 4, Pages 565-575Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200207036
Keywords
FAK; PYK2; actin cytoskeleton; focal adhesions; podosomes
Categories
Funding
- NIAMS NIH HHS [AR43225, AR47830, R01 AR043225, R01 AR047830, AR48120, P30 AR046031, R01 AR048120, P30AR46031, AR46031] Funding Source: Medline
- NINDS NIH HHS [R01 NS040480, NS40480] Funding Source: Medline
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Osteoclast activation is important for bone remodeling and is altered in multiple bone disorders. This process requires cell adhesion and extensive actin cytoskeletal reorganization. Proline-rich tyrosine kinase 2 (PYK2), a major cell adhesion-activated tyrosine kinase in osteoclasts, plays an important role in regulating this event. The mechanisms by which PYK2 regulates actin cytoskeletal organization and osteoclastic activation remain largely unknown. In this paper, we provide evidence that PYK2 directly interacts with gelsolin, an actin binding, severing, and capping protein essential for osteoclastic actin cytoskeletal organization. The interaction is mediated via the focal adhesion-targeting domain of PYK2 and an LD motif in gelsolin's COOH terminus. PYK2 phosphorylates gelsolin at tyrosine residues and regulates gelsolin bioactivity, including decreasing gelsolin binding to actin monomer and increasing gelsolin binding to phosphatidylinositol lipids. In addition, PYK2 increases actin polymerization at the fibroblastic cell periphery. Finally, PYK2 interacts with gelsolin in osteoclasts, where PYK2 activation is required for the formation of actin rings. Together, our results suggest that PYK2 is a regulator of gelsolin, revealing a novel PYK2-gelsolin pathway in regulating actin cytoskeletal organization in multiple cells, including osteoclasts.
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