| MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling. | |
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MedLine Citation:
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PMID: 20152179 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Pilar Gonzalo; Marta C Guadamillas; María Victoria Hernández-Riquer; Angela Pollán; Araceli Grande-García; Rubén A Bartolomé; Amit Vasanji; Chiara Ambrogio; Roberto Chiarle; Joaquín Teixidó; Juha Risteli; Suneel S Apte; Miguel A del Pozo; Alicia G Arroyo |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Developmental cell Volume: 18 ISSN: 1878-1551 ISO Abbreviation: Dev. Cell Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-15 Completed Date: 2010-03-19 Revised Date: 2011-07-20 |
Medline Journal Info:
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Nlm Unique ID: 101120028 Medline TA: Dev Cell Country: United States |
Other Details:
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Languages: eng Pagination: 77-89 Citation Subset: IM |
Copyright Information:
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(c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Remodeling / physiology Cell Differentiation / physiology Cell Fusion Cell Membrane / metabolism, ultrastructure Cell Movement / physiology Cell Shape / physiology Cells, Cultured Crk-Associated Substrate Protein / metabolism Giant Cells / metabolism, ultrastructure Matrix Metalloproteinase 14 / genetics, metabolism* Mice Mice, Inbred C57BL Mice, Knockout Myeloid Cells / cytology, metabolism* Osteoclasts / cytology, metabolism* Protein Structure, Tertiary / physiology Pseudopodia / metabolism, ultrastructure Signal Transduction / physiology Stem Cells / cytology, metabolism rac1 GTP-Binding Protein / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AR47074/AR/NIAMS NIH HHS; R01 AR047074-04/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bcar1 protein, mouse; 0/Crk-Associated Substrate Protein; EC 3.4.24.80/Matrix Metalloproteinase 14; EC 3.6.5.2/rac1 GTP-Binding Protein |
| Comments/Corrections | |
Comment In:
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Dev Cell. 2010 Jan 19;18(1):3-4
[PMID:
20152171
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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