title: Lasp-1 regulates podosome function.
abstract: Eukaryotic cells form a variety of adhesive structures to connect with their environment and to regulate cell motility. In contrast to classical focal adhesions, podosomes, highly dynamic structures of different cell types, are actively engaged in matrix remodelling and degradation. Podosomes are composed of an actin-rich core region surrounded by a ring-like structure containing signalling molecules, motor proteins as well as cytoskeleton-associated proteins. Lasp-1 is a ubiquitously expressed, actin-binding protein that is known to regulate cytoskeleton architecture and cell migration. This multidomain protein is predominantely present at focal adhesions, however, a second pool of Lasp-1 molecules is also found at lamellipodia and vesicle-like microdomains in the cytosol.In this report, we show that Lasp-1 is a novel component and regulator of podosomes. Immunofluorescence studies reveal a localization of Lasp-1 in the podosome ring structure, where it colocalizes with zyxin and vinculin. Life cell imaging experiments demonstrate that Lasp-1 is recruited in early steps of podosome assembly. A siRNA-mediated Lasp-1 knockdown in human macrophages affects podosome dynamics as well as their matrix degradation capacity. In summary, our data indicate that Lasp-1 is a novel component of podosomes and is involved in the regulation of podosomal function.
authors.affiliation: Medizinische Klinik D, Abteilung für Molekulare Nephrologie, Universitätsklinikum Münster, Münster, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Stölting
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiesner
authors.forename: Vanessa
authors.initials: V
authors.lastname: van Vliet
authors.forename: Elke
authors.initials: E
authors.lastname: Butt
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.forename: Stefan
authors.initials: S
authors.lastname: Linder
authors.forename: Joachim
authors.initials: J
authors.lastname: Kremerskothen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D016596:Vinculin / Q000378:metabolism; D060589:Zyxin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; C495806:Lasp1 protein, rat; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D060589:Zyxin; D016596:Vinculin