Nonchordate classic cadherins have a structurally and functionally unique domain that is absent from chordate classic cadherins.
Classic cadherins, which are adhesion molecules in cell-cell adherens junctions, have a large contribution to the construction of the animal body. Their molecular structures show clear differences between chordate and nonchordate metazoans. Although nonchordate classic cadherins have cadherin superfamily-specific extracellular repeats (CRs) and a highly conserved cytoplasmic domain (CP), these cadherins have a unique extracellular domain that is absent from vertebrate and ascidian classic cadherins. We called this the primitive classic cadherin domain (PCCD). To understand the roles of the PCCD, we constructed and characterized a series of mutant forms of the Drosophila classic cadherin DE-cadherin. Biochemical analyses indicated that the last two CRs and PCCD form a special structure with proteolytic cleavage. Mutations in the PCCD did not eliminate the cell-cell-binding function of DE-cadherin in cultured cells, but prevented the cadherin from efficiently translocating to the plasma membrane in epithelial cells of the developing embryo. In addition, genetic rescue assays suggested that although CP-mediated control plays a central role in tracheal fusion, the role of the PCCD in efficient recruitment of DE-cadherin to apical areas of the plasma membranes is also important for dynamic epithelial morphogenesis. We propose that there is a fundamental difference in the mode of classic cadherin-mediated cell-cell adhesion between chordate and nonchordate metazoans.
Oda
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Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, Kyoto Research Park, Chudoji Minami-machi, Shimogyo-ku, Kyoto, 600-8813, Japan. hoda@cell.tsukita.jst.go.jp
Tsukita
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D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila; D019143:Evolution, Molecular; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D010802:Phylogeny; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D015820:Cadherins; D018076:DNA, Complementary; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins