Drosophila α-Catenin and E-cadherin Bind to Distinct Regions of Drosophila Armadillo

Abstract

Adherens junctions are multiprotein complexes mediating cell-cell adhesion and communication. They are organized around a transmembrane cadherin, which binds a set of cytoplasmic proteins required for adhesion and to link the complex to the actin cytoskeleton. Three components of Drosophila adherens junctions, analogous to those in vertebrates, have been identified: Armadillo (homolog of ␤-catenin), Drosophila E-cadherin (DE-cadherin), and ␣-catenin. We carried out the first analysis of the interactions between these proteins using in vitro binding assays, the yeast two-hybrid system, and in vivo assays. We identified a 76-amino acid region of Armadillo that is necessary and sufficient for binding ␣ Adherens junctions consist of transmembrane cadherins and a set of cytoplasmic proteins associated with cadherin cytoplasmic domains (reviewed in Refs. 1 and 3). The extracellular domains of cadherins interact homotypically with cadherins of neighboring cells. The cytoplasmic proteins ␣-catenin, ␤-catenin, and plakoglobin (or ␥-catenin) are required for cadherin adhesive function and anchor the actin cytoskeleton. The Src tyrosine kinase substrate p120cas is also present in adherens junctions (4, 5); its function remains unknown. Changes in tyrosine phosphorylation of ␤-catenin (reviewed in Ref.2) and p120cas (6) correlate with transformation and associated changes in cell adhesion.To understand the cell biological function of adherens junctions, we must determine how interactions among different adherens junction proteins mediate assembly. ␤-Catenin and plakoglobin bind directly to the E-cadherin cytoplasmic domain in a mutually exclusive fashion (7,8). ␤-Catenin and plakoglobin are 70% identical in amino acid sequence; their central regions, containing ϳ13 copies of the 42-amino acid Arm 1 repeat (9), are particularly well conserved (ϳ80% amino acid identity). These highly conserved Arm repeats mediate interaction with cadherin (10 -12), suggesting that ␤-catenin and plakoglobin compete for the same binding site. The N-terminal regions of both ␤-catenin and plakoglobin bind to ␣-catenin; ␣-catenin does not bind cadherin directly (11,(13)(14)(15). ␣-Catenin, in turn, links adherens junctions to actin, directly (16) or via ␣-actinin (17). p120 cas also binds directly to E-cadherin (18), but likely to a site distinct from that bound by ␤-catenin/ plakoglobin (4, 5). p120cas does not interact with ␣-catenin (18), however, and thus does not appear to mediate interaction with actin. The core cadherin-catenin complex forms higher order assemblies such as the zonula adherens. Both E-and N-cadherins dimerize (19,20), and association with the cytoskeleton may help form larger assemblies.Adherens junctions were first described in vertebrates, but precisely analogous structures exist in Drosophila. The Drosophila homolog of ␤-catenin is Armadillo, first discovered because of its role in transducing the Wingless cell-cell signal (reviewed in Ref. 3). Arm is structurally similar to ␤-catenin and plakoglobin (it is 73% identical ...

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“…In Drosophila, adherens junctions consist of the same components as in vertebrates: E-cadherin (DE-cadherin), ␤-catenin, which is encoded by the segment polarity gene armadillo (arm) and ␣-catenin (Cox et al, 1996;McCartney et al, 2001;Oda and Tsukita, 1999;Pai et al, 1996;Tepass et al, 1996;Uemura et al, 1996). Arm is also an essential component of the Wingless (Wg) signaling pathway.…”

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“…Previous studies have demonstrated that bcatenin associates with the cytoplasmic domain of Ecadherin via its internal armadillo repeats (Hulsken et al, 1994;Huber and Weis, 2001). In addition, the Nterminal armadillo repeats of b-catenin associate with a-catenin, which in turn binds directly with F-actin (Pai et al, 1996). E-cadherin, a-and b-catenin do not have any SH3 domains and the associations among them are thus, not SH3-mediated.…”

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