Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin

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Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin

KA Knudsen, AP Soler, KR Johnson and MJ Wheelock
Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096, USA.

Cadherins are Ca(2+)-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, transmembrane cadherins such as E- , P-, and N-cadherin self-associate, while intracellularly they interact indirectly with the actin-based cytoskeleton. Several intracellular proteins termed catenins, including alpha-catenin, beta- catenin, and plakoglobin, are tightly associated with these cadherins and serve to link them to the cytoskeleton. Here, we present evidence that in fibroblasts alpha-actinin, but not vinculin, colocalizes extensively with the N-cadherin/catenin complex. This is in contrast to epithelial cells where both cytoskeletal proteins colocalize extensively with E-cadherin and catenins. We further show that alpha- actinin, but not vinculin, coimmunoprecipitates specifically with alpha- and beta-catenin from N- and E-cadherin-expressing cells, but only if alpha-catenin is present. Moreover, we show that alpha-actinin coimmunoprecipitates with the N-cadherin/catenin complex in an actin- independent manner. We therefore propose that cadherin/catenin complexes are linked to the actin cytoskeleton via a direct association between alpha-actinin and alpha-catenin.
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Takahashi, K., Nakanishi, H., Miyahara, M., Mandai, K., Satoh, K., Satoh, A., Nishioka, H., Aoki, J., Nomoto, A., Mizoguchi, A., Takai, Y. (1999). Nectin/PRR: An Immunoglobulin-like Cell Adhesion Molecule Recruited to Cadherin-based Adherens Junctions through Interaction with Afadin, a PDZ Domain-containing Protein. JCB 145: 539-549 [Abstract] [Full Text]
Aono, S., Nakagawa, S., Reynolds, A. B., Takeichi, M. (1999). p120ctn Acts as an Inhibitory Regulator of Cadherin Function in Colon Carcinoma Cells. JCB 145: 551-562 [Abstract] [Full Text]
Makrigiannakis, A., Coukos, G., Christofidou-Solomidou, M., Gour, B. J., Radice, G. L., Blaschuk, O., Coutifaris, C. (1999). N-Cadherin-Mediated Human Granulosa Cell Adhesion Prevents Apoptosis : A Role in Follicular Atresia and Luteolysis?. Am. J. Pathol. 154: 1391-1406 [Abstract] [Full Text]
Muller, T., Choidas, A., Reichmann, E., Ullrich, A. (1999). Phosphorylation and Free Pool of beta -Catenin Are Regulated by Tyrosine Kinases and Tyrosine Phosphatases during Epithelial Cell Migration. J. Biol. Chem. 274: 10173-10183 [Abstract] [Full Text]
Pötter, E., Bergwitz, C., Brabant, G. (1999). The Cadherin-Catenin System: Implications for Growth and Differentiation of Endocrine Tissues. Endocr. Rev. 20: 207-239 [Abstract] [Full Text]
Imamura, Y., Itoh, M., Maeno, Y., Tsukita, S., Nagafuchi, A. (1999). Functional Domains of {alpha}-Catenin Required for the Strong State of Cadherin-based Cell Adhesion. JCB 144: 1311-1322 [Abstract] [Full Text]
Mandai, K., Nakanishi, H., Satoh, A., Takahashi, K., Satoh, K., Nishioka, H., Mizoguchi, A., Takai, Y. (1999). Ponsin/SH3P12: An l-Afadin- and Vinculin-binding Protein Localized at Cell-Cell and Cell-Matrix Adherens Junctions. JCB 144: 1001-1018 [Abstract] [Full Text]
Wong, V., Ching, D., McCrea, P. D., Firestone, G. L. (1999). Glucocorticoid Down-regulation of Fascin Protein Expression Is Required for the Steroid-induced Formation of Tight Junctions and Cell-Cell Interactions in Rat Mammary Epithelial Tumor Cells. J. Biol. Chem. 274: 5443-5453 [Abstract] [Full Text]
Chen, Y.-T., Stewart, D. B., Nelson, W. J. (1999). Coupling Assembly of the E-Cadherin/{beta}-Catenin Complex to Efficient Endoplasmic Reticulum Exit and Basal-lateral Membrane Targeting of E-Cadherin in Polarized MDCK Cells. JCB 144: 687-699 [Abstract] [Full Text]