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The Catenin Family at a Glance Jcs.Biologists.Org Pierre D Cell Science at a Glance 637 The catenin family at study and discussion. The word catenin (from Catenins also act in the nucleus (Daniel, catena, latin for chain) (Ozawa et al., 1989), 2007; McCrea et al., 2009; Stepniak et al., 2009) a glance reflects the fact that some catenins contribute to (see the end of this section for references the indirect association of cadherins with the regarding -catenin). A prominent example is Pierre D. McCrea1,2,* and Dongmin b underlying actin cytoskeleton, as indicated for the stabilization of a signaling pool of -catenin Gu1,2 b b-catenin (and probably g-catenin/plakoglobin) at in response to upstream Wnt signals (e.g. Wnt 1 Department of Biochemistry and Molecular Biology, adherens junctions (Abe and Takeichi, 2008; ligands). This occurs via inhibition of a multi- University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA Pappas and Rimm, 2006). Cytoskeletal component complex that would otherwise lead 2Program in Genes and Development, University of interactions assist, for example, with the to proteasomal destruction of b-catenin Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA execution of cadherin-dependent morphogenic (Kimelman and Xu, 2006). Upon entry to the *Author for correspondence movements by facilitating the application of nucleus, b-catenin alters gene activity in a ([email protected]) contractile forces at cell-cell contact zones context-dependent manner (Arce et al., 2006; Journal of Cell Science 123, 637-642 (Gumbiner, 2005). In addition to adherens Willert and Jones, 2006). This takes place in © 2010. Published by The Company of Biologists Ltd junctions, catenins also function at desmosomes, association with transcription factors such as doi:10.1242/jcs.039842 where both plakophilins (catenins) and those from the T-cell factor (TCF) and lymphoid g-catenin/plakoglobin are involved with linkages enhancer-binding factor (LEF) protein family, Members of the catenin family were first isolated to intermediate filaments (Garrod and Chidgey, which directly bind DNA, as well as several complexed with the cytoplasmic domains of 2008; Green and Simpson, 2007; Hatzfeld, 2007; transcription and chromatin co-regulators. cadherins at cell-cell junctions, and this Schmidt and Koch, 2007). Some additional roles Varied downstream outcomes are influenced, relationship is considered one of the defining of catenins, including the modulation of cadherin extending, for example, from stem-cell aspects of catenins. Their functions at such endocytosis and small GTPases, are summarized maintenance to differentiation, and from contacts are multifaceted and remain under active later. proliferation to apoptosis (Cadigan and Peifer, The Catenin Family at a Glance jcs.biologists.org Pierre D. McCrea and Dongmin Gu What are catenins? Phylogenetic tree of catenins Signaling roles of catenins Catenins at cell-cell junctions Catenins exhibit wide-ranging functions in multiple cellular compartments. Defining features are that catenins associate with the cytoplasmic domains of Wnt cadherins, and that they contain BAR-1 (C. elegans) HMP-2 (C. elegans) a central Armadillo domain (with β the exception of α-catenin). In β-catenin p120 ARVCF p0071 Pkp-3 -catenin (human) β-catenin (mouse) accordance with their inclusion Xenopus ectoderm Xenopus ectoderm Xenopus ectoderm MCF-7 HCT8/E8 0.3 β-catenin (Xenopus) in various protein complexes, Reproduced from Hofmann et al., Reproduced from Bonné et al., 2008, with permission. 1999, with permission. 0.8 Filopodia Lamellipodia catenins modulate the functional Armadillo (Drosophila) LRP state of cell-cell junctions and Catenins in the nucleus the cytoskeleton (and thereby Plakoglobin (human) Plakophilins Plakoglobin (mouse) Dishevelled cell motility and morphology). δ In addition, they modulate the SYS-1 (C. elegans) Plakoglobin (Xenopus) -catenin ARVCF p0071 activity of genes relevant to development and disease, as 1.7 p120 p190 RhoGAP exemplified by the participation of catenins in canonical Wnt Pkp-1a Vav2 signaling. β-catenin p120 δ-catenin Pkp-1b Pkp-3 1.4 Sea urchin embryo HeLa C2C12 Human keratinocytes HCT8/E8 GSK3β Wnt pathway See accompanying article Small GTPases Reproduced from Logan et al., Reproduced from Rodova et al., Reproduced from Schmidt et al., Reproduced from Bonné et al., WRM-1 (C. elegans) for full citations. 1999, with permission. 2004, with permission. 1997, with permission. 1999, with permission. Pkp-3 (Xenopus) Journal of Cell Science APC Pkp-3 (mouse) Pkp-3 (human) Axin Cdc42 Rac1 RhoA Domain structure of human catenins Cytoplasm Pkp-2 (mouse) 0.1 NH2 Armadillo domain COOH Pkp-2 (human) WFDTDL β-catenin 1 1-12 781 Pkp-1 (mouse) β-catenin p120 Pkp-1 (human) Cytokinesis -catenin Plakoglobin 1 1-12 745 β subfamily p0071 (Xenopus) p0071 (mouse) p120 1 1-9 968 p0071 (human) DSWV δ-catenin 1 1-9 1225 δ-catenin (Xenopus) δ-catenin (mouse) Dp120 DSWV δ-catenin (human) (Drosophila) ARVCF ( Xenopus) Stress fibers 1-9 962 ARVCF (mouse) ARVCF 1 p120 (Xenopus) ARVCF (human) DSWV p120 (mouse) p120 subfamily p0071 1 1-9 1221 JAC-1 (C. elegans) p120 (human) Plakophilin-1 1 1-9 726 p120 β Plakophilin-2 1 1-9 837 -catenin β-catenin Kaiso κ Plakophilin-3 1 1-9 797 Centrosome NF B TCF Pkp subfamily p0071 - ? p120 Mutant phenotypes δ-catenin ARVCF p0071 Plakophilins Nucleus Catenin Organism Knockout (KO) or knockdown (KD) Tissue Phenotype Reference* p120 β-catenin N/A The Wnt Homepage; Grigoryan et al., 2008 Kinesin p120 Whole animal Embryonic lethality Davis and Reynolds, 2006 Blocked acinar differentiation; reduced E-cadherin levels and cell adhesion, polarity and abnormal + Salivary gland + epithelial morphology; embryonic lethality at E14 KO Mouse Reduced adherens junction components; epidermal hyperplasia and chronic inflammation in aged mice; Skin Perez-Moreno et al., 2005; Perez-Moreno p120 PLEKHA7 Nezha NFκB activation; skin neoplasias; mitotic defects et al., 2008 Microtubules p120 Dorsal forebrain Reduced spine and synapse densities; decreased cadherin levels and perturbations in Rho activities Elia et al., 2006 - δ-catenin ARVCF p0071 p120 Whole animal Disrupted gastrulation and axial elongation; reduced C-cadherin levels Fang et al., 2004 Adherens Endosome Xenopus KD (morpholino) Impaired evagination of optic vesicles and defective eye formation; perturbed cranial neural crest cell junction Anterior neural ectoderm Ciesiolka et al., 2004 migration and malformations in craniofacial cartilage p120 Mouse KO Whole animal Impaired cognitive functions; abnormal synaptic plasticity; reduced N-cadherin and PSD-95 levels Israely et al., 2004 δ -catenin Defects in gastrulation and axial elongation; cadherin reductions and Rho perturbations; Cadherin Xenopus KD (morpholino) Whole animal; anterior neural ectoderm Gu et al., 2009 malformations in craniofacial cartilage β-catenin p120 Howard Sirotkin and Raju Kucherlapati, Mouse KO Whole animal No obvious developmental defects α personal communication -catenin ARVCF Whole animal Disrupted gastrulation and axial elongation; reduced C-cadherin levels Fang et al., 2004 EPLIN Xenopus KD (morpholino) Mieke Delvaeye and Kris Vleminckx, Anterior neural ectoderm Perturbed cranial neural crest cell migration and malformations in craniofacial cartilage Plakoglobin personal communication F-actin JAC-1 C. elegans KD (RNAi) Whole animal No obvious developmental defects when depleted alone Pettitt et al., 2003 No obvious developmental defects except delayed dorsal closure Myster et al., 2003; Fox et al., 2005 p0071 Whole animal Dp120 Drosophila KO; KD (RNAi) Desmosome Defects in dorsal closure and head involution Magie et al., 2002 Plakoglobin Lysosome Peripheral nervous system Reduced numbers and density of spine-like neuronal potrusions Li et al., 2005 Desmoglein Plakophilins p0071 Not determined Desmocollin Intermediate Pkp-1 Not determined Desmoplakin filaments Pkp-2 Mouse KO Whole animal Alterations in heart morphogenesis and lethality at midgestation; dissociation of desmoplakin Grossmann et al., 2004 from junction plaques and formation of cytoplasmic granular aggregates Mouse KO Whole animal Abnormal morphology of hair follicles; reduced medullar air columns in hair shafts; altered Sklyarova et al., 2008 densities of desmosome and adherens junctions Pkp-3 Xenopus KD (morpholino) Whole animal Epidermal fragility; touch sensitivity and/or mobility defects William Munoz and Pierre McCrea, unpublished *See accompanying article for full citations. Abbreviations: ARVCF, Armadillo repeat gene deleted in velocardiofacial syndrome; APC, adenomatous polyposis coli; BAR-1, β-catenin/Armadillo-related protein 1; Cdc42, cell division cycle 42; C. elegans, Caenorhabditis elegans; Dp120, Drosophila p120-catenin; EPLIN, epithelial protein lost in neoplasm; F-actin, filamentous actin; GSK3β, glycogen synthase kinase 3β; HMP-2, humpback 2; JAC-1, juxtamembrane domain-associated catenin; LRP, LDL receptor-related protein; NFκB, nuclear factor-κB; PLEKHA7, pleckstrin homology domain-containing, family A member 7; Pkp, Plakophilin; PSD-95, postsynaptic density protein 95; Rac1, Ras-related C3 botulinum toxin substrate 1; RhoGAP, Rho GTPase-activating protein; RNAi, RNA interference; TCF, T-cell factor; Wnt, Wingless; WRM-1, worm Armadillo. © Journal of Cell Science 2010 (123, pp. 637-642) (See poster insert) 638 Journal of Cell Science 123 (5) 2009; Chien et al., 2009; Clevers, 2006; the trans-activation of genes in response to Wnt invasion than do shorter isoforms, and Grigoryan et al., 2008). 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