title: p120-independent modulation of E-cadherin adhesion activity by the membrane-proximal region of the cytoplasmic domain.
abstract: Cadherins are transmembrane glycoproteins that function as Ca2+-dependent cell-cell adhesion molecules and are linked to the actin cytoskeleton via catenins. Previously, we showed that, although E-cadherin lacking its cytoplasmic tail is active in aggregation assays, partially truncated E-cadherin lacking the carboxyl-terminal catenin-binding site is not. Contrary to this observation, a similar N-cadherin construct is found to be functional. Chimeric constructs, in which the membrane-proximal region of the partially truncated E-cadherin was replaced by that of N-cadherin, are active in aggregation assays. N-cadherin constructs in the opposite manner are nonfunctional. Although deletion of the membrane-proximal region, which eliminates the binding site for p120, results in activation of the nonfunctional E-cadherin mutant polypeptides, amino acid substitutions in the membrane-proximal region, which uncouple p120 binding, do not. The p120 uncoupling could not activate a full-length E-cadherin construct, which was beta-catenin-uncoupled by amino acid substitutions in the catenin-binding site. These results indicate that the membrane-proximal region determines the activity of these cadherin constructs but that p120 does not seem directly involved in the modulation of E-cadherin activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan. mozawa@m.kagoshima-u.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ozawa
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D002449:Cell Aggregation; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D020729:p120 GTPase Activating Protein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D018076:DNA, Complementary; D020729:p120 GTPase Activating Protein