Cell–cell junctions continue to capture the interest of cell and developmental biologists, with an emerging area being the molecular means by which junctional signals relate to gene activity in the nucleus. Although complexities often arise in determining the direct versus indirect nature of such signal transduction, it is clear that such pathways are essential for the function of tissues and that alterations may contribute to many pathological outcomes. This review assesses a variety of cell–cell junction-to-nuclear signaling pathways, and outlines interesting areas for further study.

Members of the catenin family were first isolated complexed with the cytoplasmic domains of cadherins at cell-cell junctions, and this relationship is considered one of the defining aspects of catenins. Their functions at such contacts are multifaceted and remain under active study and discussion. The word catenin (from catena, latin for chain) (Ozawa et al., 1989), reflects the fact that some catenins contribute to the indirect association of cadherins with the underlying actin cytoskeleton, as indicated for β-catenin (and probably γ-catenin/plakoglobin) at adherens junctions (Abe and Takeichi, 2008; Pappas and Rimm, 2006). Cytoskeletal interactions assist, for example, with the execution of cadherin-dependent morphogenic movements by facilitating the application of contractile forces at cell-cell contact zones (Gumbiner, 2005). In addition to adherens junctions, catenins also function at desmosomes, where both plakophilins (catenins) and γ-catenin/plakoglobin are involved with linkages to intermediate filaments (Garrod and Chidgey, 2008; Green and Simpson, 2007; Hatzfeld, 2007; Schmidt and Koch, 2007). Some additional roles of catenins, including the modulation of cadherin endocytosis and small GTPases, are summarized later.Catenins also act in the nucleus (Daniel, 2007; McCrea et al., 2009; Stepniak et al., 2009) (see the end of this section for references regarding β-catenin). A prominent example is the stabilization of a signaling pool of β-catenin in response to upstream Wnt signals (e.g. Wnt ligands). This occurs via inhibition of a multi-component complex that would otherwise lead to proteasomal destruction of β-catenin (Kimelman and Xu, 2006). Upon entry to the nucleus, β-catenin alters gene activity in a context-dependent manner (Arce et al., 2006; Willert and Jones, 2006). This takes place in association with transcription factors such as those from the T-cell factor (TCF) and lymphoid enhancer-binding factor (LEF) protein family, which directly bind DNA, as well as several transcription and chromatin co-regulators. Varied downstream outcomes are influenced, extending, for example, from stem-cell maintenance to differentiation, and from proliferation to apoptosis (Cadigan and Peifer, 2009; Chien et al., 2009; Clevers, 2006; Grigoryan et al., 2008). Given the wide biological impact of catenins, basic and translational researchers from diverse viewpoints are working to generate insights into the mechanisms that govern and execute their functions.In this poster article, we present a concise overview of the function of catenin proteins, primarily for the non-specialist. We restrict our attention to those catenins that contain an Armadillo domain [and therefore do not include the structurally unrelated α-catenin (Benjamin and Nelson, 2008; Kobielak and Fuchs, 2004)]. We direct the reader to other brief overviews (Harris and Peifer, 2005; Huelsken and Behrens, 2002; Lien et al., 2008; Macdonald et al., 2007; Reynolds, 2007), or to more in-depth reviews discussing β-catenin (Bienz, 2005; Cadigan and Peifer, 2009; Clevers, 2006; Nelson and Nusse, 2004), or the p120 or plakophilin subfamilies of catenins (Anastasiadis, 2007; Daniel, 2007; Hartsock and Nelson, 2008; Hatzfeld, 2005; Hatzfeld, 2007; Kowalczyk and Reynolds, 2004; Lien et al., 2006; McCrea et al., 2009; McCrea and Park, 2007; Perez-Moreno and Fuchs, 2006; Reynolds and Roczniak-Ferguson, 2004; van Hengel and van Roy, 2007; van Roy and McCrea, 2005; Xiao et al., 2007; Yin and Green, 2004).With the exception of the structurally unrelated α-catenin (Benjamin and Nelson, 2008; Pokutta and Weis, 2000; Scott and Yap, 2006; Yang et al., 2001), all catenins contain a central Armadillo domain that contains between nine and twelve repeats (each of roughly 40 amino acids) (Choi and Weis, 2005), which fold to produce a super-helix of helices that bears a positively charged groove and crucial binding interfaces (Huber et al., 1997; Shapiro and Weis, 2009). It is worth noting that several proteins contain Armadillo domains but do not associate with cadherins. By definition, these are not catenins; one example is α-importin, which assists in bringing proteins bearing classic nuclear localization signals into the nucleus (Peifer et al., 1994).Catenin Armadillo regions engage in numerous protein-protein interactions, and promote the association of β-catenin or p120 subfamily members with cadherins (Bienz, 2005; Meng and Takeichi, 2009; Nelson and Nusse, 2004), nuclear gene regulatory factors (Clevers, 2006) or cytoplasmic Rho-family GTPases (Anastasiadis, 2007). The N- and C-terminal domains of catenins exhibit further interesting properties: for instance, the C-terminal domain of β-catenin facilitates the trans-activation of genes in response to Wnt signaling (Arce et al., 2006; Willert and Jones, 2006).On the basis of primary sequence homology, vertebrate catenins that contain Armadillo domains are divided into three subfamilies referred to by each of three representative members: β-catenin (β-catenin, γ-catenin/plakoglobin); p120 [p120, ARVCF (Armadillo repeat gene deleted in velocardiofacial syndrome), δ-catenin, p0071]; and plakophilin (plakophilin-1 to plakophilin-3). Invertebrates have fewer catenin proteins, namely β-catenin (although variants exist in Caenorhabditis elegans) (Hardin and King, 2008; Phillips and Kimble, 2009), and a single representative of the p120 subfamily that is most similar in sequence homology to vertebrate δ-catenin.Divisions between the vertebrate catenin subfamilies are reflected at the functional level. For example, plakophilins largely associate with desmosomal cadherins, whereas members of the β-catenin or p120 subfamilies bind to classic cadherins that are present at adherens junctions. For plakophilin subfamily members, it is the N-terminal as opposed to the central Armadillo domain that binds...