Cadherin Gene Superfamily Research Articles

Characterization of N-cadherin messenger RNA and polypeptide expression in rat

The cell adhesion molecule N-cadherin is a member of the cadherin gene superfamily. The protein is involved in morphogenetic processes, including neurite extension. In this study, N-cadherin mRNA and polypeptide expression were investigated in rat brain, liver, muscle, heart, kidney and lung during postnatal development and aging. Six synthetic oligonucleotide probes covering different parts of mouse N-cadherin cDNA all hybridized to 5.2,4.3–4.4 and 3.5 kb mRNAs in rat tissues. The mRNA pattern differed between tissues and, furthermore, the amount of N-cadherin mRNA and polypeptides in brain, liver and heart was higher than in muscle, kidney and lung. N-cadherin expression decreased slightly during early postnatal development in all tissues, whereas no changes in N-cadherin expression were observed during aging.Antibodies against a fusion protein containing the transmembrane and cytoplasmic sequence of chick N-cadherin were produced. These antibodies, termed anti-N-cad-cyt, were compared to the R-156 antibodies which recognize the 24 C-terminal amino acids of N-cadherin and which have been shown to react with a broad spectrum of cadherins. Using these two antibodies, it was shown that the 130 kDa N-cadherin polypeptide was subject to calcium-dependent cleavage of the cytoplasmic domain. Conversely, in the absence of calcium the polypeptide was cleaved extracellularly, producing two C-terminal fragments of 85 and 95 kDa. A 122 kDa polypeptide was recognized by both antibodies and may be either an alternatively spliced form of N-cadherin or a closely related cadherin.

The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily

Recessive lethal mutations in the fat locus of Drosophila cause hyperplastic, tumor-like overgrowth of larval imaginal discs, defects in differentiation and morphogenesis, and death during the pupal stage. Clones of mutant cells induced by mitotic recombination demonstrate that the overgrowth phenotype is cell autonomous. Here we show that the fat locus encodes a novel member of the cadherin gene superfamily: an enormous transmembrane protein of over 5000 amino acids with a putative signal sequence, 34 tandem cadherin domains, four EGF-like repeats, a transmembrane domain, and a novel cytoplasmic domain. Two recessive lethal alleles contain alterations in the fat coding sequence, and the dominant fat allele, Gull, contains an insertion of a transposable element in the 33rd cadherin domain. Thus, this novel member of the cadherin gene superfamily functions as a tumor suppressor gene and is required for correct morphogenesis.