Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 19, Issue 1, Pages 394-404Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E07-03-0227
Keywords
-
Categories
Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [P01 CA046128, CA46128] Funding Source: Medline
- NIAMS NIH HHS [R01 AR054450, AR42927, AR54450, R01 AR042927] Funding Source: Medline
- NIDA NIH HHS [DA018343, P30 DA018343] Funding Source: Medline
- NIDDK NIH HHS [DK45735, P30 DK045735] Funding Source: Medline
- NINDS NIH HHS [R01 NS036251, NS36251, R37 NS036251] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P01CA046128] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR054450, R01AR042927] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK045735] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS036251, R37NS036251] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P30DA018343] Funding Source: NIH RePORTER
Ask authors/readers for more resources
actin. Src performs one or more unique functions in osteoclasts (OCLs), and podosome belts and bone resorption are impaired in the absence of Src. Using Src(-/-) OCLs, we investigated the specific functions of Src in the organization and dynamics of podosomes. We found that podosome number and the podosome-associated actin cloud were decreased in Src(-/-) OCLs. Videomicroscopy and fluorescence recovery after photobleaching analysis revealed that the life span of Src(-/-) podosomes was increased fourfold and that the rate of actin flux in the core was decreased by 40%. Thus, Src regulates the formation, structure, life span, and rate of actin polymerization in podosomes and in the actin cloud. Rescue of Src(-/-) OCLs with Src mutants showed that both the kinase activity and either the SH2 or the SH3 binding domain are required for Src to restore normal podosome organization and dynamics. Moreover, inhibition of Src family kinase activities in Src(-/-) OCLs by Src inhibitors or by expressing dominant-negative Src(K295M) induced the formation of abnormal podosomes. Thus, Src is an essential regulator of podosome structure, dynamics and organization.
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