Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 17, Issue 7, Pages 2882-2895Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E06-03-0187
Keywords
-
Categories
Funding
- NCI NIH HHS [P30 CA91842, P30 CA091842] Funding Source: Medline
- NIAMS NIH HHS [AR-48812, AR-46852, R01 AR046852, R01 AR048812] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007200, GM-07200, GM-38542, R01 GM038542-19, R01 GM038542] Funding Source: Medline
Ask authors/readers for more resources
Osteoclasts are essential for bone dynamics and calcium homeostasis. The cells form a tight seal on the bone surface, onto which they secrete acid and proteases to resorb bone. The seal is associated with a ring of actin filaments. Cortactin, a c-Src substrate known to promote Arp2/3-mediated actin assembly in vitro, is expressed in osteoclasts and localizes to the sealing ring. To address the role of cortactin and actin assembly in osteoclasts, we depleted cortactin by RNA interference. Cortactin-depleted osteoclasts displayed a complete loss of bone resorption with no formation of sealing zones. On nonosteoid surfaces, osteoclasts flatten with a dynamic, actin-rich peripheral edge that contains podosomes, filopodia, and lamellipodia. Cortactin depletion led to a specific loss of podosomes, revealing a tight spatial compartmentalization of actin assembly. Podosome formation was restored in cortactin-depleted cells by expression of wild-type cortactin or a Src homology 3 point mutant of cortactin. In contrast, expression of a cortactin mutant lacking tyrosine residues phosphorylated by Src did not restore podosome formation. Cortactin was found to be an early component of the nascent podosome belt, along with dynamin, supporting a role for cortactin in actin assembly.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available