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The F-actin modulator SWAP-70 controls podosome patterning in osteoclasts
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Title: | The F-actin modulator SWAP-70 controls podosome patterning in osteoclasts |
Authors: | Roscher, A. Browse this author | Hasegawa, T. Browse this author →KAKEN DB | Dohnke, S. Browse this author | Ocana-Morgner, C. Browse this author | Amizuka, N. Browse this author | Jessberger, R. Browse this author | Garbe, AI. Browse this author |
Keywords: | Actin cytoskeleton | Podosome pattering | Membrane binding | PIP3 | Swap-70 | V-ATPase |
Issue Date: | Dec-2016 |
Publisher: | Elsevier |
Journal Title: | Bone reports |
Volume: | 5 |
Start Page: | 214 |
End Page: | 221 |
Publisher DOI: | 10.1016/j.bonr.2016.07.002 |
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. |
Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/72279 |
Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 長谷川 智香
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