The uvomorulin-anchorage protein alpha catenin is a vinculin homologue.

Abstract

The cytoplasmic region of the Ca2+-dependent cell-adhesion molecule (CAM) uvomorulin associates with distinct cytoplasmic proteins with molecular masses of 102, 88, and 80 kDa termed a, (3, and ycatenin, respectively. This complex formation links uvomorulin to the actin filament network, which seems to be of primary importance for its cell-adhesion properties. We show here that antibodies against a catenin also immunoprecipitate complexes that contain human N-cadherin, mouse P-cadherin, chicken A-CAM (adherens junction-specific CAM; also called N-cadherin) or Xenopus U-cadherin, demonstrating that a catenin is complexed with other cadherins. In immunofluoresence tests, a catenin is colocalized with cadherins at the plasma membrane. However, in cadherin-negative Ltk-cells, a catenin is found uniformly distributed in the cytoplasm, suggesting some additional biological function(s). Expression of uvomorulin in these cells results in a concentration of a catenin at membrane areas ofcell contacts. We also have cloned and sequenced murine a catenin.The deduced amino acid sequence reveals a signfMcant homology to vinculin. Our results suggest the possibility of a new vinculin-related protein family involved in the cytoplasmic anchorage of cell-cell and cell-substrate adhesion molecules.The cadherin gene family of Ca2l-dependent cell adhesion molecules (CAM) was originally composed of a rather limited number of transmembrane glycoproteins of which the best studied examples were uvomorulin/E-cadherin, liver CAM (L-CAM), N-cadherin, and P-cadherin (for a review, see refs. 1 and 2). Each member was found to regulate cell adhesion of particular cell types, and this was thought to be fundamental for the organization of multicellular organisms. More recently new members of this family have been described including M-cadherin on mouse myoblasts (3), E/P-, U-, and XB-cadherin in early Xenopus development (4-6), and a new subgroup of more distantly related desmosomal glycoproteins (7-9).It has been shown that the cytoplasmic region of uvomorulin associates with defined proteins of 102, 88, and 80 kDa termed a, f3, and y catenin, respectively (10). The MATERIALS AND METHODSCell Lines. Mouse fibroblasts Ltk-, human HeLa, chicken fibroblasts CEF38, and their respective transfectants expressing mouse uvomorulin, Li-i, H1-3, and C1-4 (10, 15) were used as well as embryonal carcinoma cells F9, PCC4, and PAS5E. Porcine kidney LLC-PK7 and Xenopus A6 cells were gifts from H. Hoschutzky (Freiburg, F.R.G.) and D. Wedlich (Berlin), respectively. The A6 cells were grown in Leibovitz L-15 medium containing 8% (vol/vol) fetal calf serum (FCS) at 240C. All other cells were cultured in Dulbecco's modified Eagle's medium containing 10%o FCS at 370C in an atmosphere containing 10%6 Co2. For the generation of F9 tumors, about 1 x 107 cells were injected subcutaneously in 129/SV mice, and solid tumors were removed 12-15 days later and stored at -80TC.Puriication of a Catenin. Ten grams of solid F9 tumor was homogenized in 50 ml of No...

Adherens Junction: Molecular Architecture and Regulation

“…A key player is thought to be a-catenin, a molecule similar to vinculin (Herrenknecht et al 1991;Nagafuchi et al 1991). The a-catenin binds b-catenin, resulting in the formation of the cadherin -b-catenin -a-catenin complex.…”

The Loss of the Expression of α Catenin, the 102 kD Cadherin Associated Protein, in Central Nervous Tissues during Development

“…Anti-a catenin polyclonal antibody was previously demonstrated to recognize cy catenin in different species (11). The mAb a18 also can recognize a catenin in various species.…”

“…The expression of aN catenin was reported to be restricted to particular tissues such as nervous tissues (12). These a catenins have a similarity in sequence to vinculin, one of the major plaque proteins of cell-to-cell and cell-to-substrate adherens junction (AJ), i.e., cadherin-and integrinbased AJ (23,11,12). Taking it into consideration that vinculin may be a key protein in linking adhesion molecules (cadherins and integrins) to actin filaments (7,31), a catenins may also play an important role in the cadherin-actinfilament interaction (44).…”

p120-catenin is essential for maintenance of barrier function and intestinal homeostasis in mice

“…p120-catenin (hereafter referred to as p120) and β-catenin are armadillo repeat proteins that interact directly with distinct sites on the cadherin tail. β-catenin interacts further with α-catenin to modulate functional interactions with the actin cytoskeleton (7)(8)(9). In contrast, p120 appears to modulate the strength of cell-cell adhesion by controlling the stability and retention of E-cadherin at the cell surface (10,11).…”