title: One step ahead: role of filopodia in adhesion formation during cell migration of keratinocytes.
abstract: Cell adhesion is an essential prerequisite for cell function and movement. It depends strongly on focal adhesion complexes connecting the extracellular matrix to the actin cytoskeleton. Especially in moving cells focal adhesions are highly dynamic and believed to be formed closely behind the leading edge. Filopodia were thought to act mainly as guiding cues using their tip complexes for elongation. Here we show for keratinocytes a strong dependence of lamellipodial adhesion sites on filopodia. Upon stable contact of the VASP-containing tip spot to the substrate, a filopodial focal complex (filopodial FX) is formed right behind along the filopodia axis. These filopodial FXs are fully assembled, yet small adhesions containing all adhesion markers tested. Filopodial FXs when reached by the lamellipodium are just increased in size resulting in classical focal adhesions. At the same time most filopodia regain their elongation ability. Blocking filopodia inhibits development of new focal adhesions in the lamellipodium, while focal adhesion maturation in terms of vinculin exchange dynamics remains active. Our data therefore argue for a strong spatial and temporal dependence of focal adhesions on filopodial focal complexes in keratinocytes with filopodia not permanently initiated via new clustering of actin filaments to induce elongation.
authors.affiliation: Institute of Bio- and Nanosystems, IBN-4, Biomechanics, Research Centre Jülich, 52425 Jülich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schäfer
authors.forename: Bodo
authors.initials: B
authors.lastname: Borm
authors.forename: Simone
authors.initials: S
authors.lastname: Born
authors.forename: Christoph
authors.initials: C
authors.lastname: Möhl
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Eibl
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoffmann
mesh_terms: D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D022001:Focal Adhesions / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016608:Talin / Q000235:genetics / Q000378:metabolism; D016596:Vinculin / Q000235:genetics / Q000378:metabolism; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008840:Microfilament Proteins; D051419:Paxillin; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D016608:Talin; C092842:ZYX protein, human; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein; D016596:Vinculin