alphaT-catenin: a novel tissue-specific beta-catenin-binding protein mediating strong cell-cell adhesion.
Cadherins are major cell-cell adhesion proteins whose cytoplasmic domains bind to catenin proteins. Strong intercellular adhesion depends on linkage of the cadherin/catenin complex to the actin cytoskeleton via alpha-catenin. To date, it is not clear how different cell types achieve the variable strength of cell-cell adhesion clearly needed in a multicellular organism. Here, we report the cloning and molecular characterization of alphaT(testis)-catenin, a novel human cDNA encoding a protein with homology to both human alphaE(epithelial)-catenin and alphaN(neural)-catenin. Although originally discovered in testis, alphaT-catenin is expressed in other tissues, the highest levels being observed in heart. Immunohistochemical analysis showed human alphaT-catenin localization at intercalated discs of cardiomyocytes and in peritubular myoid cells of testis. In cells transfected with alphaT-catenin cDNA, interaction with beta-catenin was demonstrated by co-immunoprecipitation. Transfection of alpha-catenin-deficient colon carcinoma cells recruited E-cadherin and beta-catenin to cell-cell contacts and functional cadherin-mediated cell-cell adhesion was restored in this way. Moreover, compaction of these cells was at least as prominent as in the case of cells expressing endogenous alphaE-catenin. We propose that alphaT-catenin is necessary for the formation of stretch-resistant cell-cell adhesion complexes, in particular, muscle cells.
Janssens
B
B
Molecular Cell Biology Unit, Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology (VIB)-Ghent University, B-9000 Ghent, Belgium.
Goossens
S
S
Staes
K
K
Gilbert
B
B
van Hengel
J
J
Colpaert
C
C
Bruyneel
E
E
Mareel
M
M
van Roy
F
F
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism* / Q000502:physiology*; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014018:Tissue Distribution; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D016596:Vinculin / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C441963:CTNNA3 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D008164:Luminescent Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D016596:Vinculin; D049452:Green Fluorescent Proteins