ECTS2016 Poster Presentations Cell biology: osteoclasts and bone resorption (35 abstracts)
1CNRS Montpellier, CRBM, Montpellier, France; 2Montpellier University, Montpellier, France; 3Functional Proteomics Platform CNRS IGF, Montpellier, France; 4Montpellier RIO Imaging, CNRS Biocampus, Montpellier, France.
Osteoclasts resorb bone matrix through a specific adhesion structure called the sealing zone or actin ring, which is based on a belt of podosome. Much remains to be uncovered regarding the molecular mechanisms driving podosome organization into superstructures in particular the osteoclast podosome belt. Proteomic analyses in osteoclasts revealed the adaptor protein tensin 3 as 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. They associate with the osteoclast podosome belt but not with individual podosomes, contrarily 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 severe reduction in osteoclast activity. Our results suggest that Dock5 and tensin 3 cooperate for osteoclasts activity, ensuring correct podosomes organization.