title: Metalloproteinase MT1-MMP islets act as memory devices for podosome reemergence.
abstract: Podosomes are dynamic cell adhesions that are also sites of extracellular matrix degradation, through recruitment of matrix-lytic enzymes, particularly of matrix metalloproteinases. Using total internal reflection fluorescence microscopy, we show that the membrane-bound metalloproteinase MT1-MMP is enriched not only at podosomes but also at distinct "islets" embedded in the plasma membrane of primary human macrophages. MT1-MMP islets become apparent upon podosome dissolution and persist beyond podosome lifetime. Importantly, the majority of MT1-MMP islets are reused as sites of podosome reemergence. siRNA-mediated knockdown and recomplementation analyses show that islet formation is based on the cytoplasmic tail of MT1-MMP and its ability to bind the subcortical actin cytoskeleton. Collectively, our data reveal a previously unrecognized phase in the podosome life cycle and identify a structural function of MT1-MMP that is independent of its proteolytic activity. MT1-MMP islets thus act as cellular memory devices that enable efficient and localized reformation of podosomes, ensuring coordinated matrix degradation and invasion.
authors.affiliation: Institut für medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, 20246 Hamburg, Germany.
authors.forename: Karim
authors.initials: K
authors.lastname: El Azzouzi
authors.affiliation: Institut für medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, 20246 Hamburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiesner
authors.affiliation: Institut für medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, 20246 Hamburg, Germany s.linder@uke.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Linder
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D000069261:Podosomes / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D020782:Matrix Metalloproteinases; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14