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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.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.

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-1P (A, green) is colocalized with JAM-1 (red) at intestinal adherens junctions but is distinct from UNC-44 ankyrin (B) and LAD-1NP (C) localization. Arrows in A–C point to the intestinal adherens junction. Bar, 20 μm.
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fig7: LAD-1P (A, green) is colocalized with JAM-1 (red) at intestinal adherens junctions but is distinct from UNC-44 ankyrin (B) and LAD-1NP (C) localization. Arrows in A–C point to the intestinal adherens junction. Bar, 20 μm.

Mentions: LAD-1P (Fig. 4, green) by immunofluorescence is localized to polarized epithelial tissues such as the intestine and the pharynx (Fig. 4 E, i, short and long arrow, respectively), the hypodermis (Fig. 4 E, ii, arrow), and the vulva and the rectum (unpublished data). We compared the localization of LAD-1P to that of LAD-1NP and UNC-44 ankyrin in the polarized epithelia, focusing on the pharynx (Fig. 6) and the intestine (Fig. 7) . The pharynx is a single-cell–thick epithelial tube made of muscle and marginal cells, which are located with triradiate symmetry surrounding the pharyngeal lumen. The muscle and marginal cells are joined at the apices of the lumen by tight junctions thus dividing the membranes into apical and basal domains (Fig. 6 A, schematic). The apical surface (outlined in green) faces the lumen and secretes cuticle, whereas the basal surface is lined with basal lamina (White, 1988). In Fig. 6, B–D, the red signal indicates the staining pattern of JAM-1 at the adherens junctions, whereas the green signal indicates the respective staining patterns of LAD-1P, LAD-1NP, and UNC-44. In the pharynx, LAD-1P does not colocalize with JAM-1 (Fig. 6, B, iii, long arrow) but rather appears to be present in the pharyngeal apical surface (Fig. 6, B, ii, short arrows). However, because of the lack of apical pharyngeal markers further experiments have to be performed to confirm apical localization of LAD-1P. White dots were introduced to outline the pharynx in Fig. 6, B, C, iii, and D, iii, where it is difficult to discern the entire organ. On the other hand, LAD-1NP and UNC-44 ankyrin, although also expressed in the pharynx did not overlap with LAD-1P localization on the apical surface (Fig. 6, C and D).


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-1P (A, green) is colocalized with JAM-1 (red) at intestinal adherens junctions but is distinct from UNC-44 ankyrin (B) and LAD-1NP (C) localization. Arrows in A–C point to the intestinal adherens junction. Bar, 20 μm.
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Related In: Results  -  Collection

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

fig7: LAD-1P (A, green) is colocalized with JAM-1 (red) at intestinal adherens junctions but is distinct from UNC-44 ankyrin (B) and LAD-1NP (C) localization. Arrows in A–C point to the intestinal adherens junction. Bar, 20 μm.
Mentions: LAD-1P (Fig. 4, green) by immunofluorescence is localized to polarized epithelial tissues such as the intestine and the pharynx (Fig. 4 E, i, short and long arrow, respectively), the hypodermis (Fig. 4 E, ii, arrow), and the vulva and the rectum (unpublished data). We compared the localization of LAD-1P to that of LAD-1NP and UNC-44 ankyrin in the polarized epithelia, focusing on the pharynx (Fig. 6) and the intestine (Fig. 7) . The pharynx is a single-cell–thick epithelial tube made of muscle and marginal cells, which are located with triradiate symmetry surrounding the pharyngeal lumen. The muscle and marginal cells are joined at the apices of the lumen by tight junctions thus dividing the membranes into apical and basal domains (Fig. 6 A, schematic). The apical surface (outlined in green) faces the lumen and secretes cuticle, whereas the basal surface is lined with basal lamina (White, 1988). In Fig. 6, B–D, the red signal indicates the staining pattern of JAM-1 at the adherens junctions, whereas the green signal indicates the respective staining patterns of LAD-1P, LAD-1NP, and UNC-44. In the pharynx, LAD-1P does not colocalize with JAM-1 (Fig. 6, B, iii, long arrow) but rather appears to be present in the pharyngeal apical surface (Fig. 6, B, ii, short arrows). However, because of the lack of apical pharyngeal markers further experiments have to be performed to confirm apical localization of LAD-1P. White dots were introduced to outline the pharynx in Fig. 6, B, C, iii, and D, iii, where it is difficult to discern the entire organ. On the other hand, LAD-1NP and UNC-44 ankyrin, although also expressed in the pharynx did not overlap with LAD-1P localization on the apical surface (Fig. 6, C and D).

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.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.

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