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The F-actin modulator SWAP-70 controls podosome patterning in osteoclasts
- Source :
- Bone Reports, Bone Reports, Vol 5, Iss, Pp 214-221 (2016)
- Publication Year :
- 2016
- Publisher :
- Elsevier, 2016.
-
Abstract
- Osteoclasts are bone resorbing cells acting as key mediators of bone disorders. Upon adhesion to bone, osteoclasts polarize and reorganize their cytoskeleton to generate a ring-like F-actin-rich structure, the sealing zone, wherein the osteoclast's resorptive organelle, the ruffled border, is formed. The dynamic self-organization of actin-rich adhesive structures, the podosomes, from clusters to belts is crucial for osteoclast-mediated bone degradation. Mice lacking the protein SWAP-70 display an osteopetrotic phenotype due to defective bone resorption caused by impaired actin ring formation in Swap-70−/− osteoclasts. To further elucidate the mechanisms underlying this defect, we investigated the specific function of SWAP-70 in the organization and dynamics of podosomes. These detailed studies show that the transition from podosome clusters to rings is impaired in Swap-70−/− osteoclasts. Live cell imaging of dynamic F-actin turnover and SWAP-70 localization during podosome patterning indicate that SWAP-70 is dispensable for cluster formation but plays a key role in F-actin ring generation. Our data provide insights in the role of SWAP-70's F-actin binding domain and pleckstrin homology (PH) domain in the proper localization of SWAP-70 and formation of a peripheral podosome belt, respectively. Ex vivo bone analyses revealed that SWAP-70-deficient osteoclasts exhibit defective ruffled border formation and V-ATPase expression. Our findings suggest an important role of membrane binding of SWAP-70 for the regulation of actin dynamics, which is essential for podosome patterning, and thus for the resorptive activity of osteoclasts.<br />Highlights • SWAP-70 controls dynamic podosome patterning but not assembly of podosomes. • PIP3 and F-actin binding are required for proper subcellular localization of SWAP-70. • SWAP-70-deficient osteoclasts are impaired in ruffled border formation.
- Subjects :
- 0301 basic medicine
lcsh:Diseases of the musculoskeletal system
Podosome
Membrane binding
Endocrinology, Diabetes and Metabolism
V-ATPase
Biology
Bone resorption
Article
03 medical and health sciences
0302 clinical medicine
PIP3
Osteoclast
medicine
Swap-70
Orthopedics and Sports Medicine
Cytoskeleton
Actin
Actin cytoskeleton
Podosome pattering
Cell biology
Pleckstrin homology domain
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
lcsh:RC925-935
Subjects
Details
- Language :
- English
- ISSN :
- 23521872
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Bone reports
- Accession number :
- edsair.doi.dedup.....47f8eb125b3734e23157c20e2c07b9dd