Signal transduction by L1

Stable Identifier
Homo sapiens
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Besides adhesive roles in cell cell interaction, L1 functions as a signal transducing receptor providing neurons with cues from their environment for axonal growth and guidance. L1 associates with beta1 integrins on the cell surface to induce a signaling pathway involving sequential activation of pp60csrc, Vav2 -GEF, Rac1, PAK1, MEK and ERK1/2. L1 stimulates cell migration and neurite outgrowth through the MAP kinases ERK1/2. CHL1 also associates with integrins and activates a MAPK signaling pathway via pp60c-src, MEK and ERK1/2.
L1 also binds the Sema3A receptor neuropilin1 and acts as an obligate coreceptor to mediate Sema3A induced growth cone collapse and axon repulsion. This repulsion can be converted to attraction by homophilic binding of L1 on an apposing cell in trans with L1 complexed with Neuropilin1 (NP1) in the responding neuron.
L1 also interacts with FGF receptor and activates PLC gamma and DAG, resulting in the production of arachidonic acid and subsequent opening of voltage-gated channels.

Literature References
PubMed ID Title Journal Year
10818153 A MAP kinase-signaling pathway mediates neurite outgrowth on L1 and requires Src-dependent endocytosis

Schmid, RS, Pruitt, WM, Maness, PF

J Neurosci 2000
10608864 Activation of the MAPK signal cascade by the neural cell adhesion molecule L1 requires L1 internalization

Landreth, G, Schaefer, AW, Beach, CM, Kamiguchi, H, Lemmon, V, Wong, EV

J Biol Chem 1999
16597699 MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth

Gazdoiu, M, Sakurai, T, Felsenfeld, DP, Cassella, MR, Whittard, JD

Mol Biol Cell 2006
15597056 Adhesion molecule L1 stimulates neuronal migration through Vav2-Pak1 signaling

Schmid, RS, Midkiff, BR, Maness, PF, Kedar, VP

Neuroreport 2004
17189949 Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration

Schachner, M, Maness, PF

Nat Neurosci 2007
12721290 Close homolog of L1 is an enhancer of integrin-mediated cell migration

Gates, AM, Richter, M, Midkiff, BR, Buhusi, M, Maness, PF, Schachner, M

J Biol Chem 2003
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