L1 CAM is Required for Proprer Neuronal Placement Embryogenesis

Friday, June 20, 2003 - 1:00pm - 2:00pm
Lind 409
Lihsia Chen (University of Minnesota, Twin Cities)
LAD-1, the sole homologue of the L1 family of neuronal cell adhesion molecules (L1CAMs), is required for nervous system development as well as embryogenesis. Indeed, we show that mutations in lad-1 result in Unc coilers that are Egl and constipated, as well as 40% embryonic lethality. Further analysis reveals misplacement of neuronal cell bodies in the mutants.

LAD-1 contains an ankyrin binding motif, FIGQY, which allows LAD-1 to bind UNC-44 ankyrin and be linked to the spectrin-actin cytoskeleton. We show that LAD-1 is phosphorylated at the tyrosine residue of the FIGQY motif; this phosphorylation event is dependent on the egl-15 FGFR-activated Ras pathway. Phosphorylated LAD-1 is localized to axon-muscle and epithelial adherens junctions that are free of non-phosphorylated LAD-1, suggesting distinct functions for phosphorylated LAD-1. Indeed, phosphorylated L1CAMs have been reported to bind doublecortin, a microtubule-associated protein. This suggests that phosphorylation is a mechanism for LAD-1 to switch from actin to microtubule cytoskeletal linkage.

Doublecortin is thought to play a role in neuronal migration. Thus, the biochemical interaction between doublecortin and L1CAMs is particularly intriguing in light of the neuronal misplacement defects observed in the lad-1 mutant. C. elegans contains a single doublecortin homologue, zyg-8, which was previously shown to play a role in mitotic spindle positioning. We show that the zyg-8 postembryonic mutants exhibit a similar phenotype to those of the lad-1 mutant: Unc and constipated coilers as well as high levels of embryonic lethality. This result suggests that the biochemical interaction between phosphorylated L1CAMs and doublecortin is functionally significant. We are in the process of genetically assaying if zyg-8 and lad-1 functionally interact.

Recent relevant publication:

Chen, L., Ong, B., and Bennett, V. 2001. LAD-1, the C. elegans L1CAM family homologue, has essential cell adhesion roles in the early embryo, participates in cell migration, and is a substrate for phosphotyrosine-based signaling. Journal of Cell Biology 154: 841-855.