title: Plexin signaling hampers integrin-based adhesion, leading to Rho-kinase independent cell rounding, and inhibiting lamellipodia extension and cell motility.
abstract: 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.
authors.affiliation: Institute for Cancer Research and Treatment, University of Torino School of Medicine, Candiolo, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Barberis
authors.forename: S
authors.initials: S
authors.lastname: Artigiani
authors.forename: A
authors.initials: A
authors.lastname: Casazza
authors.forename: S
authors.initials: S
authors.lastname: Corso
authors.forename: S
authors.initials: S
authors.lastname: Giordano
authors.forename: C A
authors.initials: CA
authors.lastname: Love
authors.forename: E Y
authors.initials: EY
authors.lastname: Jones
authors.forename: P M
authors.initials: PM
authors.lastname: Comoglio
authors.forename: Luca
authors.initials: L
authors.lastname: Tamagnone
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D019556:COS Cells / Q000502:physiology / Q000648:ultrastructure; D002465:Cell Movement; D048429:Cell Size; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D022001:Focal Adhesions; D016023:Integrins / Q000037:antagonists & inhibitors*; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018000:Receptors, Peptide / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D039961:Semaphorins; D015398:Signal Transduction / Q000502:physiology*; D054460:rho-Associated Kinases
chemical_list: D000199:Actins; D015703:Antigens, CD; C093224:CD100 antigen; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C492114:Plxna1 protein, mouse; C492118:Plxnb1 protein, mouse; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; D039961:Semaphorins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases