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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.

Chen L, Ong B, Bennett V - J. Cell Biol. (2001)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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

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.

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LAD-1 FIGQY-tyrosine phosphorylation requires the FGFR pathway. In egl-15(n1454) homozygous- larvae (B), LAD-1P levels (green) are dramatically reduced compared with similarly arrested let-23(sy17) homozygous- larvae (A). JAM-1 immunostaining is red. Levels and localization of LAD-1NP are not affected in the egl-15 (n1454) homozygous animals (C). Bar, 10 μm.
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fig5: LAD-1 FIGQY-tyrosine phosphorylation requires the FGFR pathway. In egl-15(n1454) homozygous- larvae (B), LAD-1P levels (green) are dramatically reduced compared with similarly arrested let-23(sy17) homozygous- larvae (A). JAM-1 immunostaining is red. Levels and localization of LAD-1NP are not affected in the egl-15 (n1454) homozygous animals (C). Bar, 10 μm.

Mentions: We determined the tyrosine kinase pathway that was responsible for LAD-1 phosphorylation by screening the following tyrosine kinase-deficient or - mutants for decreased levels of phosphorylated LAD-1 (LAD-1P): vab-1 (Eph receptor kinase; George et al., 1998), kin-8 (Ror kinase; Koga et al., 1999), let-23 (EGFR; Aroian et al., 1990), and egl-15 (FGFR; DeVore et al., 1995). By immunofluorescence, LAD-1P levels were dramatically reduced only in the egl-15– background, whereas the other three kinase mutant backgrounds showed wild-type levels (Fig. 5, A and B) . Expression levels and localization of nonphosphorylated LAD-1 appeared unaltered in the egl-15– background (Fig. 5 C). This result indicates that LAD-1 FIGQY-tyrosine phosphorylation is dependent on the FGFR pathway and provides further evidence for the antibody specificity against phosphorylated FIGQY-tyrosine.


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.

Chen L, Ong B, Bennett V - J. Cell Biol. (2001)

LAD-1 FIGQY-tyrosine phosphorylation requires the FGFR pathway. In egl-15(n1454) homozygous- larvae (B), LAD-1P levels (green) are dramatically reduced compared with similarly arrested let-23(sy17) homozygous- larvae (A). JAM-1 immunostaining is red. Levels and localization of LAD-1NP are not affected in the egl-15 (n1454) homozygous animals (C). Bar, 10 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196473&req=5

fig5: LAD-1 FIGQY-tyrosine phosphorylation requires the FGFR pathway. In egl-15(n1454) homozygous- larvae (B), LAD-1P levels (green) are dramatically reduced compared with similarly arrested let-23(sy17) homozygous- larvae (A). JAM-1 immunostaining is red. Levels and localization of LAD-1NP are not affected in the egl-15 (n1454) homozygous animals (C). Bar, 10 μm.
Mentions: We determined the tyrosine kinase pathway that was responsible for LAD-1 phosphorylation by screening the following tyrosine kinase-deficient or - mutants for decreased levels of phosphorylated LAD-1 (LAD-1P): vab-1 (Eph receptor kinase; George et al., 1998), kin-8 (Ror kinase; Koga et al., 1999), let-23 (EGFR; Aroian et al., 1990), and egl-15 (FGFR; DeVore et al., 1995). By immunofluorescence, LAD-1P levels were dramatically reduced only in the egl-15– background, whereas the other three kinase mutant backgrounds showed wild-type levels (Fig. 5, A and B) . Expression levels and localization of nonphosphorylated LAD-1 appeared unaltered in the egl-15– background (Fig. 5 C). This result indicates that LAD-1 FIGQY-tyrosine phosphorylation is dependent on the FGFR pathway and provides further evidence for the antibody specificity against phosphorylated FIGQY-tyrosine.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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

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.

Show MeSH
Related in: MedlinePlus