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The Nonclustered Protocadherins

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The Cadherin Superfamily

Abstract

The protocadherins comprise the largest family of proteins within the cadherin superfamily, and are themselves further subdivided into the clustered and nonclustered protocadherins. The nonclustered protocadherins are evolutionarily conserved and vary in their regional patterns of expression within the nervous system, leading to the hypothesis that they participate in neural circuit assembly. Although the nonclustered protocadherins are strongly linked to both neurodevelopmental disorders and multiple forms of cancer, their physiological roles are poorly understood. Recent work is providing new insights into the nonclustered protocadherins, resulting in emerging themes. Here, data revealing roles for these molecules at multiple stages of development and that suggest an involvement in regulating proliferation and cell differentiation is discussed.

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References

  • Aamar E, Dawid IB (2008) Protocadherin-18a has a role in cell adhesion, behavior and migration in zebrafish development. Dev Biol 318:335–346

    Article  CAS  PubMed  Google Scholar 

  • Asad M, Wong MK, Tan TZ, Choolani M, Low J, Mori S, Virshup D, Thiery JP, Huang RY (2014) FZD7 drives in vitro aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway. Cell Death Dis 5:e1346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Babu MM, van der Lee R, de Groot NS, Gsponer J (2011) Intrinsically disordered proteins: regulation and disease. Curr Opin Struct Biol 21:432–440

    Article  CAS  PubMed  Google Scholar 

  • Berndt JD, Aoyagi A, Yang P, Anastas JN, Tang L, Moon RT (2011) Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/beta-catenin signaling. J Cell Biol 194:737–750

    Article  PubMed  PubMed Central  Google Scholar 

  • Beukers W, Hercegovac A, Vermeij M, Kandimalla R, Blok AC, van der Aa MM, Zwarthoff EC, Zuiverloon TC (2013) Hypermethylation of the polycomb group target gene PCDH7 in bladder tumors from patients of all ages. J Urol 190:311–316

    Article  CAS  PubMed  Google Scholar 

  • Biswas S, Emond MR, Jontes JD (2010) Protocadherin-19 and N-cadherin interact to control cell movements during anterior neurulation. J Cell Biol 191:1029–1041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biswas S, Emond MR, Duy PQ, Haole T, Beattie CE, Jontes JD (2014) Protocadherin-18b interacts with Nap1 to control motor axon growth and arborization in zebrafish. Mol Biol Cell 25:633–642

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Blevins CJ, Emond MR, Biswas S, Jontes JD (2011) Differential expression, alternative splicing, and adhesive properties of the zebrafish delta1-protocadherins. Neuroscience 199:523–534

    Article  CAS  PubMed  Google Scholar 

  • Bononi J, Cole A, Tewson P, Schumacher A, Bradley R (2008) Chicken protocadherin-1 functions to localize neural crest cells to the dorsal root ganglia during PNS formation. Mech Dev 125:1033–1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA, Massague J (2009) Genes that mediate breast cancer metastasis to the brain. Nature 459:1005–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bouillot S, Tillet E, Carmona G, Prandini MH, Gauchez AS, Hoffmann P, Alfaidy N, Cand F, Huber P (2011) Protocadherin-12 cleavage is a regulated process mediated by ADAM10 protein: evidence of shedding up-regulation in pre-eclampsia. J Biol Chem 286:15195–15204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bradley RS, Espeseth A, Kintner C (1998) NF-protocadherin, a novel member of the cadherin superfamily, is required for Xenopus ectodermal differentiation. Curr Biol 8:325–334

    Article  CAS  PubMed  Google Scholar 

  • Butler MG, Rafi SK, Hossain W, Stephan DA, Manzardo AM (2015) Whole exome sequencing in females with autism implicates novel and candidate genes. Int J Mol Sci 16:1312–1335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chappuis-Flament S, Wong E, Hicks LD, Kay CM, Gumbiner BM (2001) Multiple cadherin extracellular repeats mediate homophilic binding and adhesion. J Cell Biol 154:231–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen X, Gumbiner BM (2006) Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C-cadherin adhesion activity. J Cell Biol 174:301–313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen J, Lu Y, Meng S, Han MH, Lin C, Wang X (2009a) alpha- and gamma-Protocadherins negatively regulate PYK2. J Biol Chem 284:2880–2890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen X, Koh E, Yoder M, Gumbiner BM (2009b) A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis. PLoS One 4:e8411

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen Y, Londraville R, Brickner S, El-Shaar L, Fankhauser K, Dearth C, Fulton L, Sochacka A, Bhattarai S, Marrs JA, Liu Q (2013) Protocadherin-17 function in Zebrafish retinal development. Dev Neurobiol 73:259–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen B, Brinkmann K, Chen Z, Pak CW, Liao Y, Shi S, Henry L, Grishin NV, Bogdan S, Rosen MK (2014) The WAVE regulatory complex links diverse receptors to the actin cytoskeleton. Cell 156:195–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen T, Long B, Ren G, Xiang T, Li L, Wang Z, He Y, Zeng Q, Hong S, Hu G (2015a) Protocadherin20 acts as a tumor suppressor gene: epigenetic inactivation in nasopharyngeal carcinoma. J Cell Biochem 116:1766–1775

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Xiang H, Zhang Y, Wang J, Yu G (2015b) Loss of PCDH9 is associated with the differentiation of tumor cells and metastasis and predicts poor survival in gastric cancer. Clin Exp Metastasis 32:417–428

    Article  CAS  PubMed  Google Scholar 

  • Cheung HH, Lee TL, Davis AJ, Taft DH, Rennert OM, Chan WY (2010) Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer. Br J Cancer 102:419–427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chung HA, Yamamoto TS, Ueno N (2007) ANR5, an FGF target gene product, regulates gastrulation in Xenopus. Curr Biol 17:932–939

    Article  CAS  PubMed  Google Scholar 

  • Cooper SR, Emond MR, Duy PQ, Liebau BG, Wolman MA, Jontes JD (2015) Protocadherins control the modular assembly of neuronal columns in the zebrafish optic tectum. J Cell Biol 211:807–814

    Article  PubMed  PubMed Central  Google Scholar 

  • Costa VL, Henrique R, Danielsen SA, Eknaes M, Patricio P, Morais A, Oliveira J, Lothe RA, Teixeira MR, Lind GE, Jeronimo C (2011) TCF21 and PCDH17 methylation: an innovative panel of biomarkers for a simultaneous detection of urological cancers. Epigenetics 6:1120–1130

    Article  CAS  PubMed  Google Scholar 

  • Depienne C, LeGuern E (2012) PCDH19-related infantile epileptic encephalopathy: an unusual X-linked inheritance disorder. Hum Mutat 33:627–634

    Article  CAS  PubMed  Google Scholar 

  • Depienne C, Bouteiller D, Keren B, Cheuret E, Poirier K, Trouillard O, Benyahia B, Quelin C, Carpentier W, Julia S, Afenjar A, Gautier A, Rivier F, Meyer S, Berquin P, Helias M, Py I, Rivera S, Bahi-Buisson N, Gourfinkel-An I, Cazeneuve C, Ruberg M, Brice A, Nabbout R, Leguern E (2009) Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet 5:e1000381

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dibbens LM, Tarpey PS, Hynes K, Bayly MA, Scheffer IE, Smith R, Bomar J, Sutton E, Vandeleur L, Shoubridge C, Edkins S, Turner SJ, Stevens C, O'Meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Jones D, Lee R, Madison M, Mironenko T, Varian J, West S, Widaa S, Wray P, Teague J, Dicks E, Butler A, Menzies A, Jenkinson A, Shepherd R, Gusella JF, Afawi Z, Mazarib A, Neufeld MY, Kivity S, Lev D, Lerman-Sagie T, Korczyn AD, Derry CP, Sutherland GR, Friend K, Shaw M, Corbett M, Kim HG, Geschwind DH, Thomas P, Haan E, Ryan S, McKee S, Berkovic SF, Futreal PA, Stratton MR, Mulley JC, Gecz J (2008) X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat Genet 40:776–781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Emond MR, Jontes JD (2014) Bead aggregation assays for the characterization of putative cell adhesion molecules. J Vis Exp:e51762

    Google Scholar 

  • Emond MR, Biswas S, Jontes JD (2009) Protocadherin-19 is essential for early steps in brain morphogenesis. Dev Biol 334:72–83

    Article  CAS  PubMed  Google Scholar 

  • Emond MR, Biswas S, Blevins CJ, Jontes JD (2011) A complex of Protocadherin-19 and N-cadherin mediates a novel mechanism of cell adhesion. J Cell Biol 195:1115–1121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang S, Huang SF, Cao J, Wen YA, Zhang LP, Ren GS (2013) Silencing of PCDH10 in hepatocellular carcinoma via de novo DNA methylation independent of HBV infection or HBX expression. Clin Exp Med 13:127–134

    Article  CAS  PubMed  Google Scholar 

  • Giefing M, Zemke N, Brauze D, Kostrzewska-Poczekaj M, Luczak M, Szaumkessel M, Pelinska K, Kiwerska K, Tonnies H, Grenman R, Figlerowicz M, Siebert R, Szyfter K, Jarmuz M (2011) High resolution ArrayCGH and expression profiling identifies PTPRD and PCDH17/PCH68 as tumor suppressor gene candidates in laryngeal squamous cell carcinoma. Genes Chromosomes Cancer 50:154–166

    Article  CAS  PubMed  Google Scholar 

  • Gray GE, Sanes JR (1991) Migratory paths and phenotypic choices of clonally related cells in the avian optic tectum. Neuron 6:211–225

    Article  CAS  PubMed  Google Scholar 

  • Gregorio SP, Sallet PC, Do KA, Lin E, Gattaz WF, Dias-Neto E (2009) Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: preliminary evidence. Psychiatry Res 165:1–9

    Article  CAS  PubMed  Google Scholar 

  • Haruki S, Imoto I, Kozaki K, Matsui T, Kawachi H, Komatsu S, Muramatsu T, Shimada Y, Kawano T, Inazawa J (2010) Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous cell carcinoma. Carcinogenesis 31:1027–1036

    Article  CAS  PubMed  Google Scholar 

  • Hayashi S, Inoue Y, Kiyonari H, Abe T, Misaki K, Moriguchi H, Tanaka Y, Takeichi M (2014) Protocadherin-17 mediates collective axon extension by recruiting actin regulator complexes to interaxonal contacts. Dev Cell 30:673–687

    Article  CAS  PubMed  Google Scholar 

  • He D, Zeng Q, Ren G, Xiang T, Qian Y, Hu Q, Zhu J, Hong S, Hu G (2012) Protocadherin8 is a functional tumor suppressor frequently inactivated by promoter methylation in nasopharyngeal carcinoma. Eur J Cancer Prev 21:569–575

    Article  CAS  PubMed  Google Scholar 

  • Heggem MA, Bradley RS (2003) The cytoplasmic domain of Xenopus NF-protocadherin interacts with TAF1/set. Dev Cell 4:419–429

    Article  CAS  PubMed  Google Scholar 

  • Hernan R, Fasheh R, Calabrese C, Frank AJ, Maclean KH, Allard D, Barraclough R, Gilbertson RJ (2003) ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma. Cancer Res 63:140–148

    CAS  PubMed  Google Scholar 

  • Hertel N, Krishna K, Nuernberger M, Redies C (2008) A cadherin-based code for the divisions of the mouse basal ganglia. J Comp Neurol 508:511–528

    Article  PubMed  Google Scholar 

  • Hirano S, Takeichi M (2012) Cadherins in brain morphogenesis and wiring. Physiol Rev 92:597–634

    Article  CAS  PubMed  Google Scholar 

  • Hirano S, Yan Q, Suzuki ST (1999) Expression of a novel protocadherin, OL-protocadherin, in a subset of functional systems of the developing mouse brain. J Neurosci 19:995–1005

    CAS  PubMed  Google Scholar 

  • Homayouni R, Rice DS, Curran T (2001) Disabled-1 interacts with a novel developmentally regulated protocadherin. Biochem Biophys Res Commun 289:539–547

    Article  CAS  PubMed  Google Scholar 

  • Hoshina N, Tanimura A, Yamasaki M, Inoue T, Fukabori R, Kuroda T, Yokoyama K, Tezuka T, Sagara H, Hirano S, Kiyonari H, Takada M, Kobayashi K, Watanabe M, Kano M, Nakazawa T, Yamamoto T (2013) Protocadherin 17 regulates presynaptic assembly in topographic corticobasal Ganglia circuits. Neuron 78:839–854

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Sui X, Li L, Huang X, Rong R, Su X, Shi Q, Mo L, Shu X, Kuang Y, Tao Q, He C (2013) Protocadherin 17 acts as a tumour suppressor inducing tumour cell apoptosis and autophagy, and is frequently methylated in gastric and colorectal cancers. J Pathol 229:62–73

    Article  CAS  PubMed  Google Scholar 

  • Huber AH, Weis WI (2001) The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin. Cell 105:391–402

    Article  CAS  PubMed  Google Scholar 

  • Huber AH, Stewart DB, Laurents DV, Nelson WJ, Weis WI (2001) The cadherin cytoplasmic domain is unstructured in the absence of beta-catenin. A possible mechanism for regulating cadherin turnover. J Biol Chem 276:12301–12309

    Article  CAS  PubMed  Google Scholar 

  • Hulpiau P, van Roy F (2009) Molecular evolution of the cadherin superfamily. Int J Biochem Cell Biol 41:349–369

    Article  CAS  PubMed  Google Scholar 

  • Ishiyama N, Lee SH, Liu S, Li GY, Smith MJ, Reichardt LF, Ikura M (2010) Dynamic and static interactions between p120 catenin and E-cadherin regulate the stability of cell-cell adhesion. Cell 141:117–128

    Article  CAS  PubMed  Google Scholar 

  • Izuta Y, Taira T, Asayama A, Machigashira M, Kinoshita T, Fujiwara M, Suzuki ST (2015) Protocadherin-9 involvement in retinal development in Xenopus laevis. J Biochem 157:235–249

    Article  CAS  PubMed  Google Scholar 

  • Jao TM, Tsai MH, Lio HY, Weng WT, Chen CC, Tzeng ST, Chang CY, Lai YC, Yen SJ, Yu SL, Yang YC (2014) Protocadherin 10 suppresses tumorigenesis and metastasis in colorectal cancer and its genetic loss predicts adverse prognosis. Int J Cancer 135:2593–2603

    Article  CAS  PubMed  Google Scholar 

  • Kai M, Ueno N, Kinoshita N (2015) Phosphorylation-dependent ubiquitination of paraxial protocadherin (PAPC) controls gastrulation cell movements. PLoS One 10:e0115111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kasnauskiene J, Ciuladaite Z, Preiksaitiene E, Matuleviciene A, Alexandrou A, Koumbaris G, Sismani C, Pepalyte I, Patsalis PC, Kucinskas V (2012) A single gene deletion on 4q28.3: PCDH18--a new candidate gene for intellectual disability? Eur J Med Genet 55:274–277

    Article  PubMed  Google Scholar 

  • Kim SH, Yamamoto A, Bouwmeester T, Agius E, Robertis EM (1998) The role of paraxial protocadherin in selective adhesion and cell movements of the mesoderm during Xenopus gastrulation. Development 125:4681–4690

    CAS  PubMed  Google Scholar 

  • Kim SH, Jen WC, De Robertis EM, Kintner C (2000) The protocadherin PAPC establishes segmental boundaries during somitogenesis in xenopus embryos. Curr Biol 10:821–830

    Article  CAS  PubMed  Google Scholar 

  • Kim SY, Chung HS, Sun W, Kim H (2007) Spatiotemporal expression pattern of non-clustered protocadherin family members in the developing rat brain. Neuroscience 147:996–1021

    Article  CAS  PubMed  Google Scholar 

  • Kim SY, Mo JW, Han S, Choi SY, Han SB, Moon BH, Rhyu IJ, Sun W, Kim H (2010) The expression of non-clustered protocadherins in adult rat hippocampal formation and the connecting brain regions. Neuroscience 170:189–199

    Article  CAS  PubMed  Google Scholar 

  • Koning H, Sayers I, Stewart CE, de Jong D, Ten Hacken NH, Postma DS, van Oosterhout AJ, Nawijn MC, Koppelman GH (2012) Characterization of protocadherin-1 expression in primary bronchial epithelial cells: association with epithelial cell differentiation. FASEB J 26:439–448

    Article  CAS  PubMed  Google Scholar 

  • Koppelman GH, Meyers DA, Howard TD, Zheng SL, Hawkins GA, Ampleford EJ, Xu J, Koning H, Bruinenberg M, Nolte IM, van Diemen CC, Boezen HM, Timens W, Whittaker PA, Stine OC, Barton SJ, Holloway JW, Holgate ST, Graves PE, Martinez FD, van Oosterhout AJ, Bleecker ER, Postma DS (2009) Identification of PCDH1 as a novel susceptibility gene for bronchial hyperresponsiveness. Am J Respir Crit Care Med 180:929–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kraft B, Berger CD, Wallkamm V, Steinbeisser H, Wedlich D (2012) Wnt-11 and Fz7 reduce cell adhesion in convergent extension by sequestration of PAPC and C-cadherin. J Cell Biol 198:695–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krishna K, Redies C (2009) Expression of cadherin superfamily genes in brain vascular development. J Cereb Blood Flow Metab 29:224–229

    Article  CAS  Google Scholar 

  • Krishna K, Nuernberger M, Weth F, Redies C (2009) Layer-specific expression of multiple cadherins in the developing visual cortex (V1) of the ferret. Cereb Cortex 19:388–401

    Article  Google Scholar 

  • Krishna KK, Hertel N, Redies C (2011) Cadherin expression in the somatosensory cortex: evidence for a combinatorial molecular code at the single-cell level. Neuroscience 175:37–48

    Article  CAS  Google Scholar 

  • Kuroda H, Inui M, Sugimoto K, Hayata T, Asashima M (2002) Axial protocadherin is a mediator of prenotochord cell sorting in Xenopus. Dev Biol 244:267–277

    Article  CAS  PubMed  Google Scholar 

  • Lal D, Ruppert AK, Trucks H, Schulz H, de Kovel CG, Kasteleijn-Nolst Trenite D, Sonsma AC, Koeleman BP, Lindhout D, Weber YG, Lerche H, Kapser C, Schankin CJ, Kunz WS, Surges R, Elger CE, Gaus V, Schmitz B, Helbig I, Muhle H, Stephani U, Klein KM, Rosenow F, Neubauer BA, Reinthaler EM, Zimprich F, Feucht M, Moller RS, Hjalgrim H, De Jonghe P, Suls A, Lieb W, Franke A, Strauch K, Gieger C, Schurmann C, Schminke U, Nurnberg P, Consortium E, Sander T (2015) Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies. PLoS Genet 11:e1005226

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Langer MD, Guo H, Shashikanth N, Pierce JM, Leckband DE (2012) N-glycosylation alters cadherin-mediated intercellular binding kinetics. J Cell Sci 125:2478–2485

    Article  CAS  PubMed  Google Scholar 

  • Lele Z, Folchert A, Concha M, Rauch GJ, Geisler R, Rosa F, Wilson SW, Hammerschmidt M, Bally-Cuif L (2002) parachute/n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube. Development 129:3281–3294

    CAS  PubMed  Google Scholar 

  • Leshchenko VV, Kuo PY, Shaknovich R, Yang DT, Gellen T, Petrich A, Yu Y, Remache Y, Weniger MA, Rafiq S, Suh KS, Goy A, Wilson W, Verma A, Braunschweig I, Muthusamy N, Kahl BS, Byrd JC, Wiestner A, Melnick A, Parekh S (2010) Genomewide DNA methylation analysis reveals novel targets for drug development in mantle cell lymphoma. Blood 116:1025–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung LC, Urbancic V, Baudet ML, Dwivedy A, Bayley TG, Lee AC, Harris WA, Holt CE (2013) Coupling of NF-protocadherin signaling to axon guidance by cue-induced translation. Nat Neurosci 16:166–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Li W, Xie J, Wang Y, Tang A, Li X, Ye J, Gui Y, Cai Z (2011) Epigenetic inactivation of PCDH10 in human prostate cancer cell lines. Cell Biol Int 35:671–676

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Chim JC, Yang M, Ye J, Wong BC, Qiao L (2012) Role of PCDH10 and its hypermethylation in human gastric cancer. Biochim Biophys Acta 1823:298–305

    Article  CAS  PubMed  Google Scholar 

  • Li AM, Tian AX, Zhang RX, Ge J, Sun X, Cao XC (2013) Protocadherin-7 induces bone metastasis of breast cancer. Biochem Biophys Res Commun 436:486–490

    Article  CAS  PubMed  Google Scholar 

  • Lin J, Wang C, Redies C (2012) Expression of delta-protocadherins in the spinal cord of the chicken embryo. J Comp Neurol 520:1509–1531

    Article  CAS  PubMed  Google Scholar 

  • Lin YL, Li ZG, Guan TY (2013) The clinical significance of PCDH10 promoter methylation in patients with bladder transitional cell carcinoma. Urol Int 90:219–224

    Article  CAS  PubMed  Google Scholar 

  • Lin YL, Wang YL, Ma JG, Li WP (2014) Clinical significance of protocadherin 8 (PCDH8) promoter methylation in non-muscle invasive bladder cancer. J Exp Clin Cancer Res 33:68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lv J, Zhu P, Yang Z, Li M, Zhang X, Cheng J, Chen X, Lu F (2015) PCDH20 functions as a tumour-suppressor gene through antagonizing the Wnt/beta-catenin signalling pathway in hepatocellular carcinoma. J Viral Hepat 22:201–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R, Zwaigenbaum L, Roberts W, Fernandez B, Szatmari P, Scherer SW (2008) Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82:477–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Medina A, Swain RK, Kuerner KM, Steinbeisser H (2004) Xenopus paraxial protocadherin has signaling functions and is involved in tissue separation. Embo J 23:3249–3258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyake K, Hirasawa T, Soutome M, Itoh M, Goto Y, Endoh K, Takahashi K, Kudo S, Nakagawa T, Yokoi S, Taira T, Inazawa J, Kubota T (2011) The protocadherins, PCDHB1 and PCDH7, are regulated by MeCP2 in neuronal cells and brain tissues: implication for pathogenesis of Rett syndrome. BMC Neurosci 12:81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyamoto K, Fukutomi T, Akashi-Tanaka S, Hasegawa T, Asahara T, Sugimura T, Ushijima T (2005) Identification of 20 genes aberrantly methylated in human breast cancers. Int J Cancer 116:407–414

    Article  CAS  PubMed  Google Scholar 

  • Morris MR, Ricketts CJ, Gentle D, McRonald F, Carli N, Khalili H, Brown M, Kishida T, Yao M, Banks RE, Clarke N, Latif F, Maher ER (2011) Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene 30:1390–1401

    Article  CAS  PubMed  Google Scholar 

  • Morrow EM, Yoo SY, Flavell SW, Kim TK, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321:218–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mortensen LJ, Kreiner-Moller E, Hakonarson H, Bonnelykke K, Bisgaard H (2014) The PCDH1 gene and asthma in early childhood. Eur Respir J 43:792–800

    Article  CAS  PubMed  Google Scholar 

  • Mountcastle VB (1997) The columnar organization of the neocortex. Brain 120(Pt 4):701–722

    Article  PubMed  Google Scholar 

  • Murakami T, Hijikata T, Matsukawa M, Ishikawa H, Yorifuji H (2006) Zebrafish protocadherin 10 is involved in paraxial mesoderm development and somitogenesis. Dev Dyn 235:506–514

    Article  CAS  PubMed  Google Scholar 

  • Nakao S, Platek A, Hirano S, Takeichi M (2008) Contact-dependent promotion of cell migration by the OL-protocadherin-Nap1 interaction. J Cell Biol 182:395–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narayan G, Scotto L, Neelakantan V, Kottoor SH, Wong AH, Loke SL, Mansukhani M, Pothuri B, Wright JD, Kaufmann AM, Schneider A, Arias-Pulido H, Tao Q, Murty VV (2009) Protocadherin PCDH10, involved in tumor progression, is a frequent and early target of promoter hypermethylation in cervical cancer. Genes Chromosomes Cancer 48:983–992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narayan G, Freddy AJ, Xie D, Liyanage H, Clark L, Kisselev S, Un Kang J, Nandula SV, McGuinn C, Subramaniyam S, Alobeid B, Satwani P, Savage D, Bhagat G, Murty VV (2011) Promoter methylation-mediated inactivation of PCDH10 in acute lymphoblastic leukemia contributes to chemotherapy resistance. Genes Chromosomes Cancer 50:1043–1053

    Article  CAS  PubMed  Google Scholar 

  • Nguyen V, Deschet K, Henrich T, Godet E, Joly JS, Wittbrodt J, Chourrout D, Bourrat F (1999) Morphogenesis of the optic tectum in the medaka (Oryzias latipes): a morphological and molecular study, with special emphasis on cell proliferation. J Comp Neurol 413:385–404

    Article  CAS  PubMed  Google Scholar 

  • Nollet F, Kools P, van Roy F (2000) Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol 299:551–572

    Article  CAS  PubMed  Google Scholar 

  • Ozlu N, Qureshi MH, Toyoda Y, Renard BY, Mollaoglu G, Ozkan NE, Bulbul S, Poser I, Timm W, Hyman AA, Mitchison TJ, Steen JA (2015) Quantitative comparison of a human cancer cell surface proteome between interphase and mitosis. EMBO J 34:251–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pedrosa E, Shah A, Tenore C, Capogna M, Villa C, Guo X, Zheng D, Lachman HM (2010) beta-catenin promoter ChIP-chip reveals potential schizophrenia and bipolar disorder gene network. J Neurogenet 24:182–193

    Article  CAS  PubMed  Google Scholar 

  • Pfeiffer BE, Zang T, Wilkerson JR, Taniguchi M, Maksimova MA, Smith LN, Cowan CW, Huber KM (2010) Fragile X mental retardation protein is required for synapse elimination by the activity-dependent transcription factor MEF2. Neuron 66:191–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piper M, Dwivedy A, Leung L, Bradley RS, Holt CE (2008) NF-protocadherin and TAF1 regulate retinal axon initiation and elongation in vivo. J Neurosci 28:100–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rakic P (1988) Specification of cerebral cortical areas. Science 241:170–176

    Article  CAS  PubMed  Google Scholar 

  • Rashid D, Newell K, Shama L, Bradley R (2006) A requirement for NF-protocadherin and TAF1/Set in cell adhesion and neural tube formation. Dev Biol 291:170–181

    Article  CAS  PubMed  Google Scholar 

  • Redies C, Neudert F, Lin J (2011) Cadherins in cerebellar development: translation of embryonic patterning into mature functional compartmentalization. Cerebellum 10:393–408

    Article  CAS  PubMed  Google Scholar 

  • Redies C, Hertel N, Hubner CA (2012) Cadherins and neuropsychiatric disorders. Brain Res 1470:130–144

    Article  CAS  PubMed  Google Scholar 

  • Rhee J, Takahashi Y, Saga Y, Wilson-Rawls J, Rawls A (2003) The protocadherin papc is involved in the organization of the epithelium along the segmental border during mouse somitogenesis. Dev Biol 254:248–261

    Article  CAS  PubMed  Google Scholar 

  • Ryan SG, Chance PF, Zou CH, Spinner NB, Golden JA, Smietana S (1997) Epilepsy and mental retardation limited to females: an X-linked dominant disorder with male sparing. Nat Genet 17:92–95

    Article  CAS  PubMed  Google Scholar 

  • Sano K, Tanihara H, Heimark RL, Obata S, Davidson M, John TS, Taketani S, Suzuki S (1993) Protocadherins: a large family of cadherin-related molecules in central nervous system. Embo J 12:2249–2256

    CAS  PubMed  PubMed Central  Google Scholar 

  • Specchio N, Marini C, Terracciano A, Mei D, Trivisano M, Sicca F, Fusco L, Cusmai R, Darra F, Bernardina BD, Bertini E, Guerrini R, Vigevano F (2011) Spectrum of phenotypes in female patients with epilepsy due to protocadherin 19 mutations. Epilepsia 52:1251–1257

    Article  CAS  PubMed  Google Scholar 

  • Tai K, Kubota M, Shiono K, Tokutsu H, Suzuki ST (2010) Adhesion properties and retinofugal expression of chicken protocadherin-19. Brain Res 1344:13–24

    Article  CAS  PubMed  Google Scholar 

  • Tang X, Yin X, Xiang T, Li H, Li F, Chen L, Ren G (2012) Protocadherin 10 is frequently downregulated by promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer. Cancer Biomark 12:11–19

    CAS  PubMed  Google Scholar 

  • Tawk M, Araya C, Lyons DA, Reugels AM, Girdler GC, Bayley PR, Hyde DR, Tada M, Clarke JD (2007) A mirror-symmetric cell division that orchestrates neuroepithelial morphogenesis. Nature 446:797–800

    Article  CAS  PubMed  Google Scholar 

  • Tsai NP, Wilkerson JR, Guo W, Maksimova MA, DeMartino GN, Cowan CW, Huber KM (2012) Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95. Cell 151:1581–1594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uversky VN (2011) Intrinsically disordered proteins from A to Z. Int J Biochem Cell Biol 43:1090–1103

    Article  CAS  PubMed  Google Scholar 

  • Vanhalst K, Kools P, Staes K, van Roy F, Redies C (2005) delta-Protocadherins: a gene family expressed differentially in the mouse brain. Cell Mol Life Sci 62:1247–1259

    Article  CAS  PubMed  Google Scholar 

  • Vasilatos SN, Katz TA, Oesterreich S, Wan Y, Davidson NE, Huang Y (2013) Crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases mediates antineoplastic efficacy of HDAC inhibitors in human breast cancer cells. Carcinogenesis 34:1196–1207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Veerappa AM, Saldanha M, Padakannaya P, Ramachandra NB (2014) Family based genome-wide copy number scan identifies complex rearrangements at 17q21.31 in dyslexics. Am J Med Genet B Neuropsychiatr Genet 165B:572–580

    Article  PubMed  CAS  Google Scholar 

  • Vester-Christensen MB, Halim A, Joshi HJ, Steentoft C, Bennett EP, Levery SB, Vakhrushev SY, Clausen H (2013) Mining the O-mannose glycoproteome reveals cadherins as major O-mannosylated glycoproteins. Proc Natl Acad Sci U S A 110:21018–21023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Janicki P, Koster I, Berger CD, Wenzl C, Grosshans J, Steinbeisser H (2008) Xenopus Paraxial Protocadherin regulates morphogenesis by antagonizing Sprouty. Genes Dev 22:878–883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang C, Yu G, Liu J, Wang J, Zhang Y, Zhang X, Zhou Z, Huang Z (2012) Downregulation of PCDH9 predicts prognosis for patients with glioma. J Clin Neurosci 19:541–545

    Article  CAS  PubMed  Google Scholar 

  • Wang XB, Lin YL, Li ZG, Ma JH, Li J, Ma JG (2014) Protocadherin 17 promoter methylation in tumour tissue from patients with bladder transitional cell carcinoma. J Int Med Res 42:292–299

    Article  CAS  PubMed  Google Scholar 

  • Wieland I, Jakubiczka S, Muschke P, Cohen M, Thiele H, Gerlach KL, Adams RH, Wieacker P (2004) Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome. Am J Hum Genet 74:1209–1215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams EO, Sickles HM, Dooley AL, Palumbos S, Bisogni AJ, Lin DM (2011) Delta protocadherin 10 is regulated by activity in the mouse main olfactory system. Front Neural Circuits 5:9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wojtowicz WM, Flanagan JJ, Millard SS, Zipursky SL, Clemens JC (2004) Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Cell 118:619–633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolverton T, Lalande M (2001) Identification and characterization of three members of a novel subclass of protocadherins. Genomics 76:66–72

    Article  CAS  PubMed  Google Scholar 

  • Wu C, Niu L, Yan Z, Wang C, Liu N, Dai Y, Zhang P, Xu R (2015) Pcdh11x negatively regulates dendritic branching. J Mol Neurosci 56:822–828

    Article  CAS  PubMed  Google Scholar 

  • Yamagata K, Andreasson KI, Sugiura H, Maru E, Dominique M, Irie Y, Miki N, Hayashi Y, Yoshioka M, Kaneko K, Kato H, Worley PF (1999) Arcadlin is a neural activity-regulated cadherin involved in long term potentiation. J Biol Chem 274:19473–11979

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto A, Amacher SL, Kim SH, Geissert D, Kimmel CB, De Robertis EM (1998) Zebrafish paraxial protocadherin is a downstream target of spadetail involved in morphogenesis of gastrula mesoderm. Development 125:3389–3397

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yasuda S, Tanaka H, Sugiura H, Okamura K, Sakaguchi T, Tran U, Takemiya T, Mizoguchi A, Yagita Y, Sakurai T, De Robertis EM, Yamagata K (2007) Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2beta and p38 MAP kinases. Neuron 56:456–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao SW, Putti T, Murray P, Chan AT, Tao Q (2006) Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene 25:1070–1080

    Article  CAS  PubMed  Google Scholar 

  • Yoshida K (2003) Fibroblast cell shape and adhesion in vitro is altered by overexpression of the 7a and 7b isoforms of protocadherin 7, but not the 7c isoform. Cell Mol Biol Lett 8:735–741

    CAS  PubMed  Google Scholar 

  • Yoshida K, Watanabe M, Kato H, Dutta A, Sugano S (1999) BH-protocadherin-c, a member of the cadherin superfamily, interacts with protein phosphatase 1 alpha through its intracellular domain. FEBS Lett 460:93–98

    Article  CAS  PubMed  Google Scholar 

  • Yu JS, Koujak S, Nagase S, Li CM, Su T, Wang X, Keniry M, Memeo L, Rojtman A, Mansukhani M, Hibshoosh H, Tycko B, Parsons R (2008) PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer. Oncogene 27:4657–4665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Cheng YY, Tao Q, Cheung KF, Lam CN, Geng H, Tian LW, Wong YP, Tong JH, Ying JM, Jin H, To KF, Chan FK, Sung JJ (2009) Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer. Gastroenterology 136(640–651):e641

    Google Scholar 

  • Yu B, Yang H, Zhang C, Wu Q, Shao Y, Zhang J, Guan M, Wan J, Zhang W (2010) High-resolution melting analysis of PCDH10 methylation levels in gastric, colorectal and pancreatic cancers. Neoplasma 57:247–252

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Sivasankar S, Nelson WJ, Chu S (2009) Resolving cadherin interactions and binding cooperativity at the single-molecule level. Proc Natl Acad Sci U S A 106:109–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang D, Zhao W, Liao X, Bi T, Li H, Che X (2012) Frequent silencing of protocadherin 8 by promoter methylation, a candidate tumor suppressor for human gastric cancer. Oncol Rep 28:1785–1791

    CAS  PubMed  Google Scholar 

  • Zhang P, Wu C, Liu N, Niu L, Yan Z, Feng Y, Xu R (2014) Protocadherin 11 x regulates differentiation and proliferation of neural stem cell in vitro and in vivo. J Mol Neurosci 54:199–210

    Article  CAS  PubMed  Google Scholar 

  • Zhu P, Lv J, Yang Z, Guo L, Zhang L, Li M, Han W, Chen X, Zhuang H, Lu F (2014) Protocadherin 9 inhibits epithelial-mesenchymal transition and cell migration through activating GSK-3beta in hepatocellular carcinoma. Biochem Biophys Res Commun 452:567–574

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Neuroscience, Ohio State University, 1060 Carmack Road 119 Rightmire Hall, Columbus, OH, 43210, USA

    James D. Jontes

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  1. Department of Bioscience, Kwansei Gakuin University, Sanda, Hyogo, Japan

    Shintaro T. Suzuki

  2. Department of Cell Biology, Kansai Medical University, Hirakata, Osaka, Japan

    Shinji Hirano

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Jontes, J.D. (2016). The Nonclustered Protocadherins. In: Suzuki, S., Hirano, S. (eds) The Cadherin Superfamily. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56033-3_9

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