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

• Published in: The EMBO journal Vol. 27; no. 11; pp. 1549 - 1562
• Main Authors: Bechara, Ahmad, Nawabi, Homaira, Moret, Frédéric, Yaron, Avraham, Weaver, Eli, Bozon, Muriel, Abouzid, Karima, Guan, Jun-Lin, Tessier-Lavigne, Marc, Lemmon, Vance, Castellani, Valérie
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 04.06.2008; Blackwell Publishing Ltd; EMBO Press; Nature Publishing Group
• Subjects: Adhesion; Animals; axon guidance; Axons; Axons - metabolism; Biochemistry; Cell Adhesion; Cell adhesion & migration; Cellular Biology; Cerebral Cortex; Cerebral Cortex - cytology; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; focal adhesion; Focal Adhesion Protein-Tyrosine Kinases; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Genetics; Growth Cones; Growth Cones - metabolism; Life Sciences; Mice; Mice, Mutant Strains; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase 3 - metabolism; Molecular biology; Nerve Tissue Proteins; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural Cell Adhesion Molecule L1; Neural Cell Adhesion Molecule L1 - genetics; Neural Cell Adhesion Molecule L1 - metabolism; Neuropilin-1; Neuropilin-1 - metabolism; receptor; Receptors, Cell Surface; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Semaphorin-3A; Semaphorin-3A - metabolism; semaphorins; Signal Transduction
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2008.86

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.