RRC ID 3779
Author Wang X, Zhang W, Cheever T, Schwarz V, Opperman K, Hutter H, Koepp D, Chen L.
Title The C. elegans L1CAM homologue LAD-2 functions as a coreceptor in MAB-20/Sema2 mediated axon guidance.
Journal J. Cell Biol.
Abstract The L1 cell adhesion molecule (L1CAM) participates in neuronal development. Mutations in the human L1 gene can cause the neurological disorder CRASH (corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus). This study presents genetic data that shows that L1-like adhesion gene 2 (LAD-2), a Caenorhabditis elegans L1CAM, functions in axon pathfinding. In the SDQL neuron, LAD-2 mediates dorsal axon guidance via the secreted MAB-20/Sema2 and PLX-2 plexin receptor, the functions of which have largely been characterized in epidermal morphogenesis. We use targeted misexpression experiments to provide in vivo evidence that MAB-20/Sema2 acts as a repellent to SDQL. Coimmunoprecipitation assays reveal that MAB-20 weakly interacts with PLX-2; this interaction is increased in the presence of LAD-2, which can interact independently with MAB-20 and PLX-2. These results suggest that LAD-2 functions as a MAB-20 coreceptor to secure MAB-20 coupling to PLX-2. In vertebrates, L1 binds neuropilin1, the obligate receptor to the secreted Sema3A. However, invertebrates lack neuropilins. LAD-2 may thus function in the semaphorin complex by combining the roles of neuropilins and L1CAMs.
Volume 180(1)
Pages 233-46
Published 2008-1-14
DOI 10.1083/jcb.200704178
PII jcb.200704178
PMID 18195110
PMC PMC2213605
MeSH Amino Acid Sequence Animals Axons / metabolism* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Membrane Proteins / metabolism* Membrane Proteins / physiology Molecular Sequence Data Nerve Tissue Proteins / metabolism* Nerve Tissue Proteins / physiology Neural Cell Adhesion Molecule L1 / chemistry Neural Cell Adhesion Molecule L1 / genetics Neural Cell Adhesion Molecule L1 / physiology* Neural Cell Adhesion Molecules / metabolism Receptors, Cell Surface / metabolism Sequence Alignment Signal Transduction
IF 8.891
Times Cited 32
C.elegans tm3040 tm3056