The function of neuropilin/L1 complex.
L1, a cell adhesion molecule of the Ig superfamily (IgCAM) plays a critical role in the formation of neuronal networks. This is reflected by the variety of clinical signs associated with the X-linked recessive neurological disorder that is caused by mutations in the L1 gene. L1 regulates the formation of axon fascicles and promotes neurite outgrowth through interaction with a wide spectrum of binding partners including cell adhesion molecules and extra-cellular matrix components. Here we describe the emerging evidence that indicates, in addition to these well-established functions, that L1 participates in the signaling of a secreted guidance cue of the Semaphorin family, Sema3A. Three types of experimental evidence support L1 as a key component of the Sema3A receptor complex. First, L1-deficient axons do not respond to Sema3A-induced chemorepulsion. Second, L1 and NRP1, the neuropilin responsible for Sema3A binding, associate through their extracellular domains, forming a cell surface heterocomplex. Third, a soluble form of L1 modulates axonal responsiveness to Sema3A, by converting Sema3A chemorepulsion into attraction.
Castellani
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Laboratoire de Neurogenése et Morphogenèse dans le Développement et chez l'Adulte, UMR 6156, Université de la Mediterranée, IBDM, Parc Scientifique de Luminy, 13288 Marseille cedex 9, France. castellani@lgpd.univ-mrs.fr
D000818:Animals; D001369:Axons / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D020439:Growth Cones / Q000502:physiology; D006801:Humans; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000502:physiology*; D039921:Neuropilins / Q000235:genetics / Q000502:physiology*; D039961:Semaphorins / Q000502:physiology
D039842:Neural Cell Adhesion Molecule L1; D039921:Neuropilins; D039961:Semaphorins