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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 is the sole C. elegans homologue of the L1CAM family. (A) Intron-exon structure of LAD-1 (based on the cDNAs isolated). Blue boxes indicate exons. The hatched box indicates the unique 5′ coding region for the short cDNA isoform. Distinct 3′ UTRs and poly A tails of the cDNAs are also shown. Note that the shorter cDNA isoform lacks exons 1–4. (B, i) Predicted amino acid sequence for the longer lad-1 cDNA. The italicized NH2 terminus sequence in maroon indicates a predicted signal sequence peptide (SignalP; http://www.cbs.dtu.dk/services/SignalP). The ORF encodes the canonical L1CAM of six Ig domains (each Ig domain is flanked by red cysteines) followed by five fibronectin type III repeats. (Each repeat is flanked by a dark blue 5′ histidine or phenylalanine and a light blue 3′ tyrosine.) The transmembrane domain is bold and underlined, whereas the ankyrin-binding motif is highlighted in green. The last three amino acids marked in fuchsia are a consensus PDZ-binding motif. (B, ii) The pink italicized letters outline the start of the predicted signal sequence peptide for the second lad-1 isoform. The pink italicized letters in B, i, completes this signal sequence peptide. The resulting cDNA encodes for a LAD-1 isoform, which lacks the first two Ig domains. The schematics for the two LAD-1 isoforms are shown in E. (C) A phylogenetic analysis of the L1CAM family members indicates LAD-1 is not an ortholog of any one vertebrate L1CAM family member. (D) Chromosomal deficiencies stDf7 and stDf8 remove the lad-1 gene located on chromosome IV, whereas deficiencies nDf41, eDf18, and eDf19 do not.
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fig1: LAD-1 is the sole C. elegans homologue of the L1CAM family. (A) Intron-exon structure of LAD-1 (based on the cDNAs isolated). Blue boxes indicate exons. The hatched box indicates the unique 5′ coding region for the short cDNA isoform. Distinct 3′ UTRs and poly A tails of the cDNAs are also shown. Note that the shorter cDNA isoform lacks exons 1–4. (B, i) Predicted amino acid sequence for the longer lad-1 cDNA. The italicized NH2 terminus sequence in maroon indicates a predicted signal sequence peptide (SignalP; http://www.cbs.dtu.dk/services/SignalP). The ORF encodes the canonical L1CAM of six Ig domains (each Ig domain is flanked by red cysteines) followed by five fibronectin type III repeats. (Each repeat is flanked by a dark blue 5′ histidine or phenylalanine and a light blue 3′ tyrosine.) The transmembrane domain is bold and underlined, whereas the ankyrin-binding motif is highlighted in green. The last three amino acids marked in fuchsia are a consensus PDZ-binding motif. (B, ii) The pink italicized letters outline the start of the predicted signal sequence peptide for the second lad-1 isoform. The pink italicized letters in B, i, completes this signal sequence peptide. The resulting cDNA encodes for a LAD-1 isoform, which lacks the first two Ig domains. The schematics for the two LAD-1 isoforms are shown in E. (C) A phylogenetic analysis of the L1CAM family members indicates LAD-1 is not an ortholog of any one vertebrate L1CAM family member. (D) Chromosomal deficiencies stDf7 and stDf8 remove the lad-1 gene located on chromosome IV, whereas deficiencies nDf41, eDf18, and eDf19 do not.

Mentions: The C. elegans genome contains a single gene homologous to the vertebrate L1 family of neuronal adhesion molecules (Hutter et al., 2000; Teichmann and Chothia, 2000) (Fig. 1, C and D) . We isolated cDNAs encoding two LAD-1 isoforms by a combination of 5′ rapid amplification of cDNA ends and screening of a C. elegans mixed stage cDNA library (Fig. 1, A, B, and E). One isoform encodes an LAD-1 protein, which shares the canonical L1CAM structure (for review see Hortsch, 1996) of six extracellular Ig domains linked to five fibronectin type III repeats followed by a transmembrane domain and a cytoplasmic tail, containing the ankyrin-binding motif, FIGQY (Fig. 1 E). The second isoform, a result of an alternative splicing event, encodes a shorter LAD-1 protein that has a unique signal sequence peptide and lacks the first two Ig domains (Fig. 1, B and E).


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 is the sole C. elegans homologue of the L1CAM family. (A) Intron-exon structure of LAD-1 (based on the cDNAs isolated). Blue boxes indicate exons. The hatched box indicates the unique 5′ coding region for the short cDNA isoform. Distinct 3′ UTRs and poly A tails of the cDNAs are also shown. Note that the shorter cDNA isoform lacks exons 1–4. (B, i) Predicted amino acid sequence for the longer lad-1 cDNA. The italicized NH2 terminus sequence in maroon indicates a predicted signal sequence peptide (SignalP; http://www.cbs.dtu.dk/services/SignalP). The ORF encodes the canonical L1CAM of six Ig domains (each Ig domain is flanked by red cysteines) followed by five fibronectin type III repeats. (Each repeat is flanked by a dark blue 5′ histidine or phenylalanine and a light blue 3′ tyrosine.) The transmembrane domain is bold and underlined, whereas the ankyrin-binding motif is highlighted in green. The last three amino acids marked in fuchsia are a consensus PDZ-binding motif. (B, ii) The pink italicized letters outline the start of the predicted signal sequence peptide for the second lad-1 isoform. The pink italicized letters in B, i, completes this signal sequence peptide. The resulting cDNA encodes for a LAD-1 isoform, which lacks the first two Ig domains. The schematics for the two LAD-1 isoforms are shown in E. (C) A phylogenetic analysis of the L1CAM family members indicates LAD-1 is not an ortholog of any one vertebrate L1CAM family member. (D) Chromosomal deficiencies stDf7 and stDf8 remove the lad-1 gene located on chromosome IV, whereas deficiencies nDf41, eDf18, and eDf19 do not.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196473&req=5

fig1: LAD-1 is the sole C. elegans homologue of the L1CAM family. (A) Intron-exon structure of LAD-1 (based on the cDNAs isolated). Blue boxes indicate exons. The hatched box indicates the unique 5′ coding region for the short cDNA isoform. Distinct 3′ UTRs and poly A tails of the cDNAs are also shown. Note that the shorter cDNA isoform lacks exons 1–4. (B, i) Predicted amino acid sequence for the longer lad-1 cDNA. The italicized NH2 terminus sequence in maroon indicates a predicted signal sequence peptide (SignalP; http://www.cbs.dtu.dk/services/SignalP). The ORF encodes the canonical L1CAM of six Ig domains (each Ig domain is flanked by red cysteines) followed by five fibronectin type III repeats. (Each repeat is flanked by a dark blue 5′ histidine or phenylalanine and a light blue 3′ tyrosine.) The transmembrane domain is bold and underlined, whereas the ankyrin-binding motif is highlighted in green. The last three amino acids marked in fuchsia are a consensus PDZ-binding motif. (B, ii) The pink italicized letters outline the start of the predicted signal sequence peptide for the second lad-1 isoform. The pink italicized letters in B, i, completes this signal sequence peptide. The resulting cDNA encodes for a LAD-1 isoform, which lacks the first two Ig domains. The schematics for the two LAD-1 isoforms are shown in E. (C) A phylogenetic analysis of the L1CAM family members indicates LAD-1 is not an ortholog of any one vertebrate L1CAM family member. (D) Chromosomal deficiencies stDf7 and stDf8 remove the lad-1 gene located on chromosome IV, whereas deficiencies nDf41, eDf18, and eDf19 do not.
Mentions: The C. elegans genome contains a single gene homologous to the vertebrate L1 family of neuronal adhesion molecules (Hutter et al., 2000; Teichmann and Chothia, 2000) (Fig. 1, C and D) . We isolated cDNAs encoding two LAD-1 isoforms by a combination of 5′ rapid amplification of cDNA ends and screening of a C. elegans mixed stage cDNA library (Fig. 1, A, B, and E). One isoform encodes an LAD-1 protein, which shares the canonical L1CAM structure (for review see Hortsch, 1996) of six extracellular Ig domains linked to five fibronectin type III repeats followed by a transmembrane domain and a cytoplasmic tail, containing the ankyrin-binding motif, FIGQY (Fig. 1 E). The second isoform, a result of an alternative splicing event, encodes a shorter LAD-1 protein that has a unique signal sequence peptide and lacks the first two Ig domains (Fig. 1, B and E).

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