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oai:repisalud.isciii.es:20.500.12105/271792026-01-28T01:16:45Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Gonzalo, Pilar author Guadamillas, Marta C author Hernández-Riquer, María Victoria author Pollán, Angela author Grande-García, Araceli author Bartolomé, Rubén A author Vasanji, Amit author Ambrogio, Chiara author Chiarle, Roberto author Teixidó, Joaquín author Risteli, Juha author Apte, Suneel S author del Pozo, Miguel A author Arroyo, Alicia G author 2010-01-19 Cell fusion is essential for fertilization, myotube formation, and inflammation. Macrophages fuse under various circumstances, but the molecular signals involved in the distinct steps of their fusion are not fully characterized. Using null mice and derived cells, we show that the protease MT1-MMP is necessary for macrophage fusion during osteoclast and giant-cell formation in vitro and in vivo. Specifically, MT1-MMP is required for lamellipodia formation and for proper cell morphology and motility of bone marrow myeloid progenitors prior to membrane fusion. These functions of MT1-MMP do not depend on MT1-MMP catalytic activity or downstream pro-MMP-2 activation. Instead, MT1-MMP null cells show a decreased Rac1 activity and reduced membrane targeting of Rac1 and the adaptor protein p130Cas. Retroviral rescue experiments and protein binding assays delineate a signaling pathway in which MT1-MMP, via its cytosolic tail, contributes to macrophage migration and fusion by regulating Rac1 activity through an association with p130Cas. Dev Cell. 2010 Jan 19;18(1):77-89. Developmental Cell 20152179 https://hdl.handle.net/20.500.12105/27179 MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling.