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  • The EMBO Journal (2008) 27, 1549 - 1562
  • doi:10.1038/emboj.2008.86

Published online: 8 May 2008

FAK–MAPK-dependent adhesion disassembly downstream of L1 contributes to semaphorin3A-induced collapse

Ahmad Bechara1, Homaira Nawabi1, Frédéric Moret1, Avraham Yaron2, Eli Weaver3, Muriel Bozon1, Karima Abouzid1, Jun-Lin Guan4, Marc Tessier-Lavigne2, Vance Lemmon3 and Valérie Castellani1

  1. Université de Lyon, Centre de Génétique Moléculaire et Cellulaire (CGMC) UMR CNRS 5534, Villeurbanne, France
  2. University of San Francisco, Genentech Inc., San Francisco, CA, USA
  3. The Miami Project to Cure Paralysis, University of Miami, Miami, FL, USA
  4. Cornell University, Ithaca, NY, USA

Correspondence to:

Valérie Castellani, University of Lyon, CGMC-UMR-CNRS 5534, Universite Claude Bernard Lyon1, 43 bd 11 Novembre, Villeurbanne 69622, France. Tel.: +33 0472 43 26 91; Fax: +33 0472 43 26 85; E-mail: castellani@cgmc.univ-lyon1.fr

Received 15 June 2007; Accepted 4 April 2008

Axonal receptors for class 3 semaphorins (Sema3s) are heterocomplexes of neuropilins (Nrps) and Plexin-As signalling coreceptors. In the developing cerebral cortex, the Ig superfamily cell adhesion molecule L1 associates with Nrp1. Intriguingly, the genetic removal of L1 blocks axon responses of cortical neurons to Sema3A in vitro despite the expression of Plexin-As in the cortex, suggesting either that L1 substitutes for Plexin-As or that L1 and Plexin-A are both required and mediate distinct roles. We report that association of Nrp1 with L1 but not Plexin-As mediates the recruitment and activation of a Sema3A-induced focal adhesion kinase–mitogen-activated protein kinase cascade. This signalling downstream of L1 is needed for the disassembly of adherent points formed in growth cones and subsequently their collapse response to Sema3A. Plexin-As and L1 are coexpressed and present in common complexes in cortical neurons and both dominant-negative forms of Plexin-A and L1 impair their response to Sema3A. Consistently, Nrp1-expressing cortical projections are defective in mice lacking Plexin-A3, Plexin-A4 or L1. This reveals that specific signalling activities downstream of L1 and Plexin-As cooperate for mediating the axon guidance effects of Sema3A.

  • Keywords:

    • axon guidance,
    • cerebral cortex,
    • focal adhesion,
    • receptor,
    • semaphorins