biostudies-literatureDufrancais OFondation Toulouse Cancer SantéNIAID NIH HHSEuropean Molecular Biology LaboratoryFrench National Research AgencyInstitut National de la Santé et de la Recherche MédicaleFondation pour la recherche contre le cancerCIHRFoundation F. Initiativas par Fondation Fonroga ToulouseINSERMToulouse Université Paul SabatierLa Ligue contre le CancerUniversité Toulouse III - Paul Sabatier (UT3)National Health & Medical Research Council of AustraliaCentre National de la Recherche ScientifiqueFondation pour la Recherche MédicaleNIAMS NIH HHSWellcome TrustToulouse Université, La Ligue contre le cancer par Toulouse Université, CARe doctoral schoolNIGMS NIH HHSNIH HHSe202409169https://www.ebi.ac.uk/biostudies/studies/S-EPMC12558046biostudies-literatureUnknown224(11)Cell-cell fusion is an evolutionarily conserved process that is essential for many functions, including the formation of bone-resorbing multinucleated osteoclasts. Osteoclast multinucleation involves dynamic interactions between the actin cytoskeleton and the plasma membrane that are still poorly characterized. We found that moesin, a cytoskeletal linker protein member of the Ezrin, radixin, and moesin (ERM) protein family, plays a critical role in both osteoclast fusion and function. Moesin inhibition favors osteoclast multinucleation as well as HIV-1- and inflammation-induced cell fusion. Accordingly, moesin depletion decreases membrane-to-cortex attachment and enhances the formation of tunneling nanotubes, F-actin-based intercellular bridges triggering cell-cell fusion. In addition, moeThe Journal of cell biologyMoesin controls cell-cell fusion and osteoclast function.PMC12558046P30 AR069619EQU202303016313ANR-18-EURE-0003ANR DFG 2020 JA-3038/2-1APP2029078APP2020097ANR16-CE13-0005-01ANR-10-INBS-04PJT-1620109ANR-20-CE14-0037R01 AI147118K12 GM0812592K12GM081259-16Plozza MHalper JSanchez TDufrancais OBlin-Wakkach CBen Neji MBordignon PJJuzans MArnaud GBurkhardt JKCarreno SMaridonneau-Parini IPavlos NJDiz-Munoz ABoerckel JDVerollet CRaynaud-Messina BMascarau RGence RBergert MMonard SCVerdys PLagarrigue FMetais APanebianco CJPoincloux RLe Cabec VfalseMoesin controls cell-cell fusion and osteoclast function.Cell-cell fusion is an evolutionarily conserved process that is essential for many functions, including the formation of bone-resorbing multinucleated osteoclasts. Osteoclast multinucleation involves dynamic interactions between the actin cytoskeleton and the plasma membrane that are still poorly characterized. We found that moesin, a cytoskeletal linker protein member of the Ezrin, radixin, and moesin (ERM) protein family, plays a critical role in both osteoclast fusion and function. Moesin inhibition favors osteoclast multinucleation as well as HIV-1- and inflammation-induced cell fusion. Accordingly, moesin depletion decreases membrane-to-cortex attachment and enhances the formation of tunneling nanotubes, F-actin-based intercellular bridges triggering cell-cell fusion. In addition, moe2025-01-01T00:00:00Z2025 Nov2026-07-15T14:31:42.152Z2026-07-06T03:08:46.593ZS-EPMC125580464114365110.1083/jcb.202409169