Recycling pathway of L1

Stable Identifier
Homo sapiens
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L1 functions in many aspects of neuronal development including axon outgrowth and neuronal migration. These functions require coordination between L1 and the actin cytoskeleton. F-actin continuously moves in a retrograde direction from the P-(peripheral) domain of the growth cone towards the growth cone's C-(central) domain. L1, attached to the actin cytoskeleton via membrane cytoskeletal linkers (MCKs) such as ankyrins (Ankyrin-G, -B and -R) and members of the ERMs (ezrin, radixin, and moesin) family, link this retrograde F-actin flow with extracellular immobile ligands.
Forward translocation of growth cone requires not only the CAM-actin linkage but also a gradient of cell substrate adhesion (strong adhesion at the front and weak adhesion at the rear) so that the cytoskeletal machinery is able to pull the cell forward as attachments at the rear are released. This asymmetry is achieved in part by internalizing L1 molecules as they are moved to the rear of the growth cone coupled to retrograde F-actin flow and recycling them to the leading edge plasma membrane.
L1 internalization is mediated by phosphorylation and dephosphorylation. The L1 cytoplasmic domain (L1CD) carries an endocytic or sorting motif, YRSLE, that is recognized by the clathrin associated adaptor protein-2 (AP-2). AP-2 binds the YRSLE motif only when its tyrosine is not phosphorylated and triggers L1 endocytosis. SRC kinase associated with lipid rafts in the P-domain membrane phosphorylates L1 molecules on tyrosine-1176, stabilizing them in the plasma membrane. L1 endocytosis is triggered by the dephosphorylation of Y1176 within the C domain. Some of these internalized L1 molecules are transported in an anterograde direction along microtubules for reuse in the leading edge.

Literature References
PubMed ID Title Journal Year
14709786 The mechanism of axon growth: what we have learned from the cell adhesion molecule L1

Kamiguchi, H

Mol Neurobiol 2003
10804209 Recycling of the cell adhesion molecule L1 in axonal growth cones

Kamiguchi, H, Lemmon, V

J Neurosci 2000
11717353 The role of endocytic l1 trafficking in polarized adhesion and migration of nerve growth cones

Kamiguchi, H, Yoshihara, F

J Neurosci 2001
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