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FAK–MAPK‐dependent adhesion disassembly downstream of L1 contributes to semaphorin3A‐induced collapse
Author(s) -
Bechara Ahmad,
Nawabi Homaira,
Moret Frédéric,
Yaron Avraham,
Weaver Eli,
Bozon Muriel,
Abouzid Karima,
Guan JunLin,
TessierLavigne Marc,
Lemmon Vance,
Castellani Valérie
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.86
Subject(s) - semaphorin , plexin , sema3a , neuropilin 1 , biology , axon guidance , microbiology and biotechnology , growth cone , kinase , neuropilin , neuroscience , signal transduction , receptor , axon , genetics , cancer research , vascular endothelial growth factor , vegf receptors
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.