Tensin 3 is a new partner of Dock5 that controls osteoclast podosome organization and activity
| Autor: | Sylvain de Rossi, Julio Mateos-Langerak, Anne Blangy, Heiani Touaitahuata, Anne Morel, Serge Urbach |
|---|---|
| Přispěvatelé: | Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BOUBLIK, Yvan, Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BioCampus (BCM) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
rho GTP-Binding Proteins
0301 basic medicine musculoskeletal diseases Podosome Osteoclasts macromolecular substances [SDV.BC]Life Sciences [q-bio]/Cellular Biology Bone resorption Mice 03 medical and health sciences Imaging Three-Dimensional Protein Domains Osteoclast Tensins [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology medicine Animals Guanine Nucleotide Exchange Factors Humans Tensin [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Gene Silencing Bone Resorption [SDV.BC] Life Sciences [q-bio]/Cellular Biology Actin Microscopy biology Dock5 Signal transducing adaptor protein Cell Biology Vinculin Dock rac GTP-Binding Proteins Cell biology Mice Inbred C57BL Protein Transport HEK293 Cells RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure Podosomes biology.protein Adhesion Protein Binding |
| Zdroj: | Journal of Cell Science Journal of Cell Science, Company of Biologists, 2016, 129 (18), pp.3449--3461. ⟨10.1242/jcs.184622⟩ Journal of Cell Science, 2016, 129 (18), pp.3449--3461. ⟨10.1242/jcs.184622⟩ |
| ISSN: | 0021-9533 1477-9137 |
| DOI: | 10.1242/jcs.184622⟩ |
| Popis: | International audience; Bone resorption by osteoclasts is mediated by a typical adhesion structure called the sealing zone or actin ring, whose architecture is based on a belt of podosomes. The molecular mechanisms driving podosome organization into superstructures remain poorly understood to date, in particular at the osteoclast podosome belt. We performed proteomic analyses in osteoclasts and found that the adaptor protein tensin 3 is a partner of Dock5, a Rac exchange factor necessary for podosome belt formation and bone resorption. Expression of tensin 3 and Dock5 concomitantly increase during osteoclast differentiation. These proteins associate with the osteoclast podosome belt but not with individual podosomes, in contrast to vinculin. Super-resolution microscopy revealed that, even if they colocalize in the x-y plane of the podosome belt, Dock5 and tensin 3 differentially localize relative to vinculin in the z-axis. Tensin 3 increases Dock5 exchange activity towards Rac, and suppression of tensin 3 in osteoclasts destabilizes podosome organization, leading to delocalization of Dock5 and a severe reduction in osteoclast activity. Our results suggest that Dock5 and tensin 3 cooperate for osteoclast activity, to ensure the correct organization of podosomes. |
| Databáze: | OpenAIRE |
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