Identification and Characterization of a Soluble Cadherin-7 Isoform Produced by Alternative Splicing

Abstract

We identified an alternative mRNA encoding a novel cadherin-7 isoform by reverse transcriptase-PCR of RNA from day 12 chicken embryos. The alternative mRNA contains 49 bases of insertion in the premembrane region, leading to the substitution of 14 amino acids and the introduction of a premature stop codon. Identification of a 49-bp insertion sequence in the genomic DNA corresponding to the intron of the cadherin-7 gene suggests that alternative splicing is the cause of the alternative mRNA. Transient expression of the variant form in COS-7 or 293 cells produced a soluble protein. Aggregation assays and immunoprecipitation showed that the variant protein interacts with full-length cadherin-7 in vitro and in vivo and inhibits full-length cadherin-7-mediated cell adhesion. Immunohistochemistry revealed that the variant form was strongly expressed in dermomyotomes rather than in migrating neural crest cells, in contrast to the full-length cadherin-7, suggesting differential regulation of splicing and possible roles of variant cadherin-7 in the development of dermomyotomes and other tissues.

A secreted form of P-cadherin is expressed in malignant melanoma

“…However, other members of the cadherin superfamily as protocadherins are known to exist in multiple mRNA isoforms [22]. For classical cadherins, recently an alternatively spliced form of cadherin 11 was found in breast carcinoma [23] and a cadherin-7 isoform in chicken embryogenesis [24] both resulting in soluble cadherins lacking the transmembrane and cytoplasmatic region. Exactly the same is seen in P-cadherin in melanoma, which also lacks the C-terminus consisting of the transmembrane and cytoplasmatic region and its Nterminus is discharged from the cell as can be seen in cell culture supernatant (Fig.…”

Extracellular Cleavage of Cadherin-11 by ADAM Metalloproteases Is Essential forXenopusCranial Neural Crest Cell Migration

“…Similarly, cadherin-7 was shown to have a rapid turnover rate in migrating neural crest cells when compared with N-cadherin (Dufour et al, 1999). This turnover is likely due to proteolysis as shown in cell culture experiments, but the enzyme responsible for this proteolysis remains to be identified (Kawano et al, 2002). Thus, the pairing of selected ADAM metalloproteases with cadherins may provide them with unique properties such as promoting cellular migration.…”

Involvement of cadherins 7 and 20 in mouse embryogenesis and melanocyte transformation

“…Cad7 is most similar to Cad20 (61.4% identity), and the respective genes are linked on the long arm of human chromosome 18q22-23 and in a syntenic region of murine chromosome 1 (Faulkner-Jones et al, 1999). An alternatively spliced cdh7 cDNA has been isolated from chicken (Kawano et al, 2002). This cDNA has a 49 bp insertion in the MPED, resulting in the production of a soluble Cad7.…”