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FASEB Journal

Publication date: 2004-03
Volume: 18 Pages: 592 -
ISSN: 0892-6638, 1530-6860 PMID: 14734633
DOI: 10.1096/fj.03-0957fje
Publisher: The Federation of American Societies for Experimental Biology


Barberis, D
Artigiani, S ; Casazza, Andrea ; Corso, S ; Giordano, S ; Love, CA ; Jones, EY ; Comoglio, PM ; Tamagnone, Luca


Actins, Animals, Antigens, CD, Axons, COS Cells, Cell Movement, Cell Size, Cercopithecus aethiops, Cytoskeleton, Focal Adhesions, Integrins, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Mice, Nerve Tissue Proteins, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Pseudopodia, Receptors, Cell Surface, Receptors, Peptide, Recombinant Fusion Proteins, Semaphorins, Signal Transduction, rho-Associated Kinases, 0601 Biochemistry and Cell Biology, 0606 Physiology, 1116 Medical Physiology, Biochemistry & Molecular Biology


Plexins encode receptors for semaphorins, molecular signals guiding cell migration, and axon pathfinding. The mechanisms mediating plexin function are poorly understood. Plexin activation in adhering cells rapidly leads to retraction of cellular processes and cell rounding "cell collapse"). Here we show that, unexpectedly, this response does not require the activity of Rho-dependent kinase (ROCK) nor the contraction of F-actin cables. Interestingly, integrin-based focal adhesive structures are disassembled within minutes upon plexin activation; this is followed by actin depolymerization and, eventually, by cellular collapse. We also show that plexin activation hinders cell attachment to adhesive substrates, blocks the extension of lamellipodia, and thereby inhibits cell migration. We conclude that plexin signaling uncouples cell substrate-adhesion from cytoskeletal dynamics required for cell migration and axon extension.