title: Tensin 3 is a new partner of Dock5 that controls osteoclast podosome organization and activity.
abstract: 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.
authors: CRBM, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 34000 Montpellier, France Montpellier University, 34000 Montpellier, France.
authors: Heiani
authors: H
authors: Touaitahuata
authors: CRBM, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 34000 Montpellier, France Montpellier University, 34000 Montpellier, France.
authors: Anne
authors: A
authors: Morel
authors: Montpellier University, 34000 Montpellier, France Functional Proteomics Platform, Institut de Génomique Fonctionnelle, CNRS UMR 5203, 34000 Montpellier, France.
authors: Serge
authors: S
authors: Urbach
authors: Montpellier University, 34000 Montpellier, France Montpellier RIO Imaging, Biocampus UMS3426 CNRS, 34000 Montpellier, France.
authors: Julio
authors: J
authors: Mateos-Langerak
authors: Montpellier University, 34000 Montpellier, France Montpellier RIO Imaging, Biocampus UMS3426 CNRS, 34000 Montpellier, France.
authors: Sylvain
authors: S
authors: de Rossi
authors: CRBM, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 34000 Montpellier, France Montpellier University, 34000 Montpellier, France anne.blangy@crbm.cnrs.fr.
authors: Anne
authors: 0000-0001-7043-0784
authors: A
authors: Blangy
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000473:pathology; D020868:Gene Silencing; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D010010:Osteoclasts / Q000378:metabolism*; D000069261:Podosomes / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D021381:Protein Transport; D000067996:RAW 264.7 Cells; D000070876:Tensins / Q000737:chemistry / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: C531318:Dock5 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D000070876:Tensins; D016596:Vinculin; C500779:Tns3 protein, mouse; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins
keywords: Actin; Adhesion; Dock; Osteoclast; Podosome; Tensin