title: LAD-1, the Caenorhabditis elegans L1CAM homologue, participates in embryonic and gonadal morphogenesis and is a substrate for fibroblast growth factor receptor pathway-dependent phosphotyrosine-based signaling.
abstract: This study shows that L1-like adhesion (LAD-1), the sole Caenorhabditis elegans homologue of the L1 family of neuronal adhesion molecules, is required for proper development of the germline and the early embryo and embryonic and gonadal morphogenesis. In addition, the ubiquitously expressed LAD-1, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in multiple tissues at sites of cell-cell contact. Finally, we show that LAD-1 is phosphorylated in a fibroblast growth factor receptor (FGFR) pathway-dependent manner on a tyrosine residue in the highly conserved ankyrin-binding motif, FIGQY, which was shown previously to abolish the L1 family of cell adhesion molecule (L1CAM) binding to ankyrin in cultured cells. Immunofluorescence studies revealed that FIGQY-tyrosine-phosphorylated LAD-1 does not colocalize with nonphosphorylated LAD-1 or UNC-44 ankyrin but instead is localized to sites that undergo mechanical stress in polarized epithelia and axon-body wall muscle junctions. These findings suggest a novel ankyrin-independent role for LAD-1 related to FGFR signaling. Taken together, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.
authors.affiliation: Howard Hughes Medical Institute, Department of Cell Biology, and Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. l.chen@cellbio.duke.edu
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Ong
authors.forename: V
authors.initials: V
authors.lastname: Bennett
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000302:isolation & purification; D001369:Axons; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology; D006066:Gonads / Q000254:growth & development*; D015801:Helminth Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007365:Intercellular Junctions / Q000648:ultrastructure; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000235:genetics*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009024:Morphogenesis; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D017487:Ankyrins; D029742:Caenorhabditis elegans Proteins; D015816:Cell Adhesion Molecules, Neuronal; D015801:Helminth Proteins; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; C501528:SAX-7 protein, C elegans; D019000:Phosphotyrosine