Identification of the region of alpha-catenin that plays an essential role in cadherin-mediated cell adhesion.
alpha-Catenin is an intrinsic component of the cadherin adhesion complex and is a 102-kDa protein with multiple interaction sites, including homodimerization sites, and binding sites for beta- and gamma-catenin (plakoglobin), alpha-actinin, and actin. Besides the binding to beta- or gamma-catenin, it is unknown, however, which interaction is critical for the function of cadherins. By expressing a series of E-cadherin-alpha-catenin chimeric molecules on leukemia cells (K562), we have identified the region of alpha-catenin that confers aggregation inducing activity to nonfunctional tail-less E-cadherin. The region has been mapped to the carboxyl-terminal 295 amino acids of alpha-catenin. Consistent with this result, expression in alpha-catenin-deficient cells (DLD-1/Delta alpha) of a mutant alpha-catenin molecule consisting of the amino-terminal beta-/gamma-catenin-binding site and the carboxyl-terminal cell adhesion region identified in the above experiments induced E-cadherin-mediated cell aggregation and compaction. Cells expressing E-cadherin chimeric molecules with the homologous carboxyl-terminal region of vinculin, which contains the actin-binding site of vinculin, did not, however, aggregate as strongly as ones expressing E-cadherin-alpha-catenin chimeric molecules.
Ozawa
M
M
Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan. mozawa@med2.fufm.kagoshima-u.ac.jp
D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051178:alpha Catenin
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin