A role for alphabeta1 integrins in focal adhesion function and polarized cytoskeletal dynamics.
alphabeta1 integrins have been implicated in the survival, spreading, and migration of cells and tissues. To explore the underlying biology, we identified conditions where primary beta1 null keratinocytes adhere, proliferate, and display robust alphavbeta6 integrin-induced, peripheral focal contacts associated with elaborate stress fibers. Mechanistically, this appears to be due to reduced FAK and Src and elevated RhoA and Rock activities. Visualization on a genetic background of GFPactin shows that beta1 null keratinocytes spread, but do so aberrantly, and when induced to migrate from skin explants in vitro, the cells are not able to rapidly reorient their actin cytoskeleton toward the polarized movement. As judged by RFPzyxin/GFPactin videomicroscopy, the alphavbeta6-actin network does not undergo efficient turnover. Without the ability to remodel their integrin-actin network efficiently, alphabeta1-deficient keratinocytes cannot respond dynamically to their environment and polarize movements.
Raghavan
Srikala
S
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University,New York, NY 10021, USA. fuchslb@rockefeller.edu
Vaezi
Alec
A
Fuchs
Elaine
E
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000295:instrumentation / Q000379:methods; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010590:Phalloidine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D019737:Transplants; D014443:Tyrosine / Q000378:metabolism
D000199:Actins; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D005353:Fibronectins; D018398:Homeodomain Proteins; D007211:Indoles; D016023:Integrins; D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D014157:Transcription Factors; D010590:Phalloidine; D014443:Tyrosine; C007293:DAPI; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse