3k5r Citations

T-cadherin structures reveal a novel adhesive binding mechanism.

Abstract

Vertebrate genomes encode 19 classical cadherins and about 100 nonclassical cadherins. Adhesion by classical cadherins depends on binding interactions in their N-terminal EC1 domains, which swap N-terminal beta-strands between partner molecules from apposing cells. However, strand-swapping sequence signatures are absent from nonclassical cadherins, raising the question of how these proteins function in adhesion. Here, we show that T-cadherin, a glycosylphosphatidylinositol (GPI)-anchored cadherin, forms dimers through an alternative nonswapped interface near the EC1-EC2 calcium-binding sites. Mutations within this interface ablate the adhesive capacity of T-cadherin. These nonadhesive T-cadherin mutants also lose the ability to regulate neurite outgrowth from T-cadherin-expressing neurons. Our findings reveal the likely molecular architecture of the T-cadherin homophilic interface and its requirement for axon outgrowth regulation. The adhesive binding mode used by T-cadherin may also be used by other nonclassical cadherins.

Articles - 3k5r mentioned but not cited (1)

  1. T-cadherin structures reveal a novel adhesive binding mechanism. Ciatto C, Bahna F, Zampieri N, VanSteenhouse HC, Katsamba PS, Ahlsen G, Harrison OJ, Brasch J, Jin X, Posy S, Vendome J, Ranscht B, Jessell TM, Honig B, Shapiro L. Nat. Struct. Mol. Biol. 17 339-347 (2010)


Reviews citing this publication (15)

  1. Thinking outside the cell: how cadherins drive adhesion. Brasch J, Harrison OJ, Honig B, Shapiro L. Trends Cell Biol. 22 299-310 (2012)
  2. Cadherins in brain morphogenesis and wiring. Hirano S, Takeichi M. Physiol. Rev. 92 597-634 (2012)
  3. Cadherin adhesion and mechanotransduction. Leckband DE, de Rooij J. Annu. Rev. Cell Dev. Biol. 30 291-315 (2014)
  4. Cadherin 13 in cancer. Andreeva AV, Kutuzov MA. Genes Chromosomes Cancer 49 775-790 (2010)
  5. Impact of the ADHD-susceptibility gene CDH13 on development and function of brain networks. Rivero O, Sich S, Popp S, Schmitt A, Franke B, Lesch KP. Eur Neuropsychopharmacol 23 492-507 (2013)
  6. Cadherin recognition and adhesion. Leckband D, Sivasankar S. Curr. Opin. Cell Biol. 24 620-627 (2012)
  7. Classical and desmosomal cadherins at a glance. Saito M, Tucker DK, Kohlhorst D, Niessen CM, Kowalczyk AP. J. Cell. Sci. 125 2547-2552 (2012)
  8. Sorting out a promiscuous superfamily: towards cadherin connectomics. Sotomayor M, Gaudet R, Corey DP. Trends Cell Biol. 24 524-536 (2014)
  9. Curious cases: Altered dose-response relationships in addiction genetics. Uhl GR, Drgonova J, Hall FS. Pharmacol. Ther. 141 335-346 (2014)
  10. Cadherin-based transsynaptic networks in establishing and modifying neural connectivity. Friedman LG, Benson DL, Huntley GW. Curr. Top. Dev. Biol. 112 415-465 (2015)
  11. Human cell adhesion molecules: annotated functional subtypes and overrepresentation of addiction-associated genes. Zhong X, Drgonova J, Li CY, Uhl GR. Ann. N. Y. Acad. Sci. 1349 83-95 (2015)
  12. Adhesion Protein Structure, Molecular Affinities, and Principles of Cell-Cell Recognition. Honig B, Shapiro L. Cell 181 520-535 (2020)
  13. Biophysical basis of cadherin mediated cell-cell adhesion. Priest AV, Shafraz O, Sivasankar S. Exp. Cell Res. 358 10-13 (2017)
  14. Structural origins of clustered protocadherin-mediated neuronal barcoding. Rubinstein R, Goodman KM, Maniatis T, Shapiro L, Honig B. Semin. Cell Dev. Biol. 69 140-150 (2017)
  15. Engineering the Interactions of Classical Cadherin Cell-Cell Adhesion Proteins. Sivasankar S, Xie B. J Immunol 211 343-349 (2023)

Articles citing this publication (58)

  1. T-cadherin is critical for adiponectin-mediated cardioprotection in mice. Denzel MS, Scimia MC, Zumstein PM, Walsh K, Ruiz-Lozano P, Ranscht B. J. Clin. Invest. 120 4342-4352 (2010)
  2. Ideal, catch, and slip bonds in cadherin adhesion. Rakshit S, Zhang Y, Manibog K, Shafraz O, Sivasankar S. Proc. Natl. Acad. Sci. U.S.A. 109 18815-18820 (2012)
  3. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci. Børglum AD, Demontis D, Grove J, Pallesen J, Hollegaard MV, Pedersen CB, Hedemand A, Mattheisen M, GROUP investigators10, Uitterlinden A, Nyegaard M, Ørntoft T, Wiuf C, Didriksen M, Nordentoft M, Nöthen MM, Rietschel M, Ophoff RA, Cichon S, Yolken RH, Hougaard DM, Mortensen PB, Mors O. Mol. Psychiatry 19 325-333 (2014)
  4. Molecular design principles underlying β-strand swapping in the adhesive dimerization of cadherins. Vendome J, Posy S, Jin X, Bahna F, Ahlsen G, Shapiro L, Honig B. Nat. Struct. Mol. Biol. 18 693-700 (2011)
  5. Mammal-restricted elements predispose human RET to folding impairment by HSCR mutations. Kjaer S, Hanrahan S, Totty N, McDonald NQ. Nat. Struct. Mol. Biol. 17 726-731 (2010)
  6. Structure of the N terminus of cadherin 23 reveals a new adhesion mechanism for a subset of cadherin superfamily members. Elledge HM, Kazmierczak P, Clark P, Joseph JS, Kolatkar A, Kuhn P, Müller U. Proc. Natl. Acad. Sci. U.S.A. 107 10708-10712 (2010)
  7. Structural Basis of Diverse Homophilic Recognition by Clustered α- and β-Protocadherins. Goodman KM, Rubinstein R, Thu CA, Bahna F, Mannepalli S, Ahlsén G, Rittenhouse C, Maniatis T, Honig B, Shapiro L. Neuron 90 709-723 (2016)
  8. Cadherin-13, a risk gene for ADHD and comorbid disorders, impacts GABAergic function in hippocampus and cognition. Rivero O, Selten MM, Sich S, Popp S, Bacmeister L, Amendola E, Negwer M, Schubert D, Proft F, Kiser D, Schmitt AG, Gross C, Kolk SM, Strekalova T, van den Hove D, Resink TJ, Nadif Kasri N, Lesch KP. Transl Psychiatry 5 e655 (2015)
  9. Structural and energetic determinants of adhesive binding specificity in type I cadherins. Vendome J, Felsovalyi K, Song H, Yang Z, Jin X, Brasch J, Harrison OJ, Ahlsen G, Bahna F, Kaczynska A, Katsamba PS, Edmond D, Hubbell WL, Shapiro L, Honig B. Proc. Natl. Acad. Sci. U.S.A. 111 E4175-84 (2014)
  10. RET recognition of GDNF-GFRα1 ligand by a composite binding site promotes membrane-proximal self-association. Goodman KM, Kjær S, Beuron F, Knowles PP, Nawrotek A, Burns EM, Purkiss AG, George R, Santoro M, Morris EP, McDonald NQ. Cell Rep 8 1894-1904 (2014)
  11. Nanomechanics of the cadherin ectodomain: "canalization" by Ca2+ binding results in a new mechanical element. Oroz J, Valbuena A, Vera AM, Mendieta J, Gómez-Puertas P, Carrión-Vázquez M. J. Biol. Chem. 286 9405-9418 (2011)
  12. Functional properties of rare missense variants of human CDH13 found in adult attention deficit/hyperactivity disorder (ADHD) patients. Mavroconstanti T, Johansson S, Winge I, Knappskog PM, Haavik J. PLoS ONE 8 e71445 (2013)
  13. Crystal structures of Drosophila N-cadherin ectodomain regions reveal a widely used class of Ca²+-free interdomain linkers. Jin X, Walker MA, Felsövályi K, Vendome J, Bahna F, Mannepalli S, Cosmanescu F, Ahlsen G, Honig B, Shapiro L. Proc. Natl. Acad. Sci. U.S.A. 109 E127-34 (2012)
  14. Cadherin-13 is a critical regulator of GABAergic modulation in human stem-cell-derived neuronal networks. Mossink B, van Rhijn JR, Wang S, Linda K, Vitale MR, Zöller JEM, van Hugte EJH, Bak J, Verboven AHA, Selten M, Negwer M, Latour BL, van der Werf I, Keller JM, Klein Gunnewiek TM, Schoenmaker C, Oudakker A, Anania A, Jansen S, Lesch KP, Frega M, van Bokhoven H, Schubert D, Nadif Kasri N. Mol Psychiatry 27 1-18 (2022)
  15. T-cadherin (Cdh13) in association with pancreatic β-cell granules contributes to second phase insulin secretion. Tyrberg B, Miles P, Azizian KT, Denzel MS, Nieves ML, Monosov EZ, Levine F, Ranscht B. Islets 3 327-337 (2011)
  16. Cell adhesion molecules: druggable targets for modulating the connectome and brain disorders? Uhl GR, Drgonova J. Neuropsychopharmacology 39 235 (2014)
  17. Loss of T-cadherin (CDH-13) regulates AKT signaling and desensitizes cells to apoptosis in melanoma. Bosserhoff AK, Ellmann L, Quast AS, Eberle J, Boyle GM, Kuphal S. Mol. Carcinog. 53 635-647 (2014)
  18. O-glycosylation of the non-canonical T-cadherin from rabbit skeletal muscle by single mannose residues. Winterhalter PR, Lommel M, Ruppert T, Strahl S. FEBS Lett. 587 3715-3721 (2013)
  19. Structural determinants of adhesion by Protocadherin-19 and implications for its role in epilepsy. Cooper SR, Jontes JD, Sotomayor M. Elife 5 (2016)
  20. Engineering domain-swapped binding interfaces by mutually exclusive folding. Ha JH, Karchin JM, Walker-Kopp N, Huang LS, Berry EA, Loh SN. J. Mol. Biol. 416 495-502 (2012)
  21. The unique prodomain of T-cadherin plays a key role in adiponectin binding with the essential extracellular cadherin repeats 1 and 2. Fukuda S, Kita S, Obata Y, Fujishima Y, Nagao H, Masuda S, Tanaka Y, Nishizawa H, Funahashi T, Takagi J, Maeda N, Shimomura I. J. Biol. Chem. 292 7840-7849 (2017)
  22. An elastic element in the protocadherin-15 tip link of the inner ear. Araya-Secchi R, Neel BL, Sotomayor M. Nat Commun 7 13458 (2016)
  23. Cadherin 13: human cis-regulation and selectively-altered addiction phenotypes and cerebral cortical dopamine in knockout mice. Drgonova J, Walther D, Hartstein GL, Bukhari MO, Baumann MH, Katz J, Hall FS, Arnold ER, Flax S, Riley A, Rivero-Martin O, Lesch KP, Troncoso J, Ranscht B, Uhl GR. Mol. Med. 22 537-547 (2016)
  24. Cross-talk between EGFR and T-cadherin: EGFR activation promotes T-cadherin localization to intercellular contacts. Kyriakakis E, Maslova K, Frachet A, Ferri N, Contini A, Pfaff D, Erne P, Resink TJ, Philippova M. Cell. Signal. 25 1044-1053 (2013)
  25. LI-cadherin cis-dimerizes in the plasma membrane Ca(2+) independently and forms highly dynamic trans-contacts. Bartolmäs T, Hirschfeld-Ihlow C, Jonas S, Schaefer M, Geßner R. Cell. Mol. Life Sci. 69 3851-3862 (2012)
  26. Protective role of Cadherin 13 in interneuron development. Killen AC, Barber M, Paulin JJW, Ranscht B, Parnavelas JG, Andrews WD. Brain Struct Funct 222 3567-3585 (2017)
  27. Genome-wide association analysis of avian resistance to Campylobacter jejuni colonization identifies risk locus spanning the CDH13 gene. Connell S, Meade KG, Allan B, Lloyd AT, Downing T, O'Farrelly C, Bradley DG. G3 (Bethesda) 3 881-890 (2013)
  28. Spontaneous dimerization of titin protein Z1Z2 domains induces strong nanomechanical anchoring. Garcia-Manyes S, Badilla CL, Alegre-Cebollada J, Javadi Y, Fernández JM. J. Biol. Chem. 287 20240-20247 (2012)
  29. T-cadherin association with clinicopathological features and prognosis in axillary lymph node-positive breast cancer. Kong DD, Yang J, Li L, Wang W, Chen YN, Wang SB, Zhou YZ. Breast Cancer Res. Treat. 150 119-126 (2015)
  30. Alpha-1 antitrypsin inhibits RANKL-induced osteoclast formation and functions. Akbar MA, Nardo D, Chen MJ, Elshikha AS, Ahamed R, Elsayed EM, Bigot C, Holliday LS, Song S. Mol. Med. 23 57-69 (2017)
  31. E-cadherin binds to desmoglein to facilitate desmosome assembly. Shafraz O, Rübsam M, Stahley SN, Caldara AL, Kowalczyk AP, Niessen CM, Sivasankar S. Elife 7 (2018)
  32. Kinetic Measurements Reveal Enhanced Protein-Protein Interactions at Intercellular Junctions. Shashikanth N, Kisting MA, Leckband DE. Sci Rep 6 23623 (2016)
  33. Multiple dimeric structures and strand-swap dimerization of E-cadherin in solution visualized by high-speed atomic force microscopy. Nishiguchi S, Furuta T, Uchihashi T. Proc Natl Acad Sci U S A 119 e2208067119 (2022)
  34. Structural and thermodynamic characterization of the self-adhesive properties of human P-cadherin. Kudo S, Caaveiro JM, Miyafusa T, Goda S, Ishii K, Matsuura T, Sudou Y, Kodama T, Hamakubo T, Tsumoto K. Mol Biosyst 8 2050-2053 (2012)
  35. Differential Spatiotemporal Expression of Type I and Type II Cadherins Associated With the Segmentation of the Central Nervous System and Formation of Brain Nuclei in the Developing Mouse. Polanco J, Reyes-Vigil F, Weisberg SD, Dhimitruka I, Brusés JL. Front Mol Neurosci 14 633719 (2021)
  36. Elastic versus brittle mechanical responses predicted for dimeric cadherin complexes. Neel BL, Nisler CR, Walujkar S, Araya-Secchi R, Sotomayor M. Biophys J 121 1013-1028 (2022)
  37. Molecular determinants of cadherin ideal bond formation: Conformation-dependent unbinding on a multidimensional landscape. Manibog K, Sankar K, Kim SA, Zhang Y, Jernigan RL, Sivasankar S. Proc. Natl. Acad. Sci. U.S.A. 113 E5711-20 (2016)
  38. The extracellular juncture domains in the intimin passenger adopt a constitutively extended conformation inducing restraints to its sphere of action. Weikum J, Kulakova A, Tesei G, Yoshimoto S, Jægerum LV, Schütz M, Hori K, Skepö M, Harris P, Leo JC, Morth JP. Sci Rep 10 21249 (2020)
  39. Adiponectin and Its Receptors Are Differentially Expressed in Human Tissues and Cell Lines of Distinct Origin. Jasinski-Bergner S, Büttner M, Quandt D, Seliger B, Kielstein H. Obes Facts 10 569-583 (2017)
  40. Cadherins mediate sequential roles through a hierarchy of mechanisms in the developing mammillary body. Szabó NE, Haddad-Tóvolli R, Zhou X, Alvarez-Bolado G. Front Neuroanat 9 29 (2015)
  41. Crystal structure of the nonclassical cadherin-17 N-terminus and implications for its adhesive binding mechanism. Gray ME, Sotomayor M. Acta Crystallogr F Struct Biol Commun 77 85-94 (2021)
  42. Regulation of nerve growth and patterning by cell surface protein disulphide isomerase. Cook GM, Sousa C, Schaeffer J, Wiles K, Jareonsettasin P, Kalyanasundaram A, Walder E, Casper C, Patel S, Chua PW, Riboni-Verri G, Raza M, Swaddiwudhipong N, Hui A, Abdullah A, Wajed S, Keynes RJ. Elife 9 (2020)
  43. Structural basis of the strong cell-cell junction formed by cadherin-23. Singaraju GS, Sagar A, Kumar A, Samuel JS, Hazra JP, Sannigrahi MK, Yennamalli RM, Ashish F, Rakshit S. FEBS J (2019)
  44. T-cadherin is associated with prognosis in triple-negative breast cancer. Kong DD, Wang MH, Yang J, Li L, Wang W, Wang SB, Zhou YZ. Oncol Lett 14 2975-2981 (2017)
  45. A Mechanically Weak Extracellular Membrane-Adjacent Domain Induces Dimerization of Protocadherin-15. De-la-Torre P, Choudhary D, Araya-Secchi R, Narui Y, Sotomayor M. Biophys. J. 115 2368-2385 (2018)
  46. Analysis of GPI-Anchored Receptor Distribution and Dynamics in Live Cells by Tag-mediated Enzymatic Labeling and FRET. Balatskaya MN, Baglay AI, Rubtsov YP, V Sharonov G. Methods Protoc 3 (2020)
  47. Association of T-cadherin levels with the response to neoadjuvant chemotherapy in locally advanced breast cancer. Kong D, Wang MH, Yang J, Li L. Oncotarget 8 13747-13753 (2017)
  48. CDH1 Mutation Distribution and Type Suggests Genetic Differences between the Etiology of Orofacial Clefting and Gastric Cancer. Selvanathan A, Nixon CY, Zhu Y, Scietti L, Forneris F, Uribe LMM, Lidral AC, Jezewski PA, Mulliken JB, Murray JC, Buckley MF, Cox TC, Roscioli T. Genes (Basel) 11 (2020)
  49. CDH13 promoter methylation regulates cisplatin resistance of non-small cell lung cancer cells. Wang Y, Zhang L, Yang J, Li B, Wang J. Oncol Lett 16 5715-5722 (2018)
  50. Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain. Forero A, Rivero O, Wäldchen S, Ku HP, Kiser DP, Gärtner Y, Pennington LS, Waider J, Gaspar P, Jansch C, Edenhofer F, Resink TJ, Blum R, Sauer M, Lesch KP. Front Cell Neurosci 11 307 (2017)
  51. Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors. Tantra M, Guo L, Kim J, Zainolabidin N, Eulenburg V, Augustine GJ, Chen AI. Genes Brain Behav. 17 e12466 (2018)
  52. Cryo-EM structure of rhinovirus C15a bound to its cadherin-related protein 3 receptor. Sun Y, Watters K, Hill MG, Fang Q, Liu Y, Kuhn RJ, Klose T, Rossmann MG, Palmenberg AC. Proc Natl Acad Sci U S A 117 6784-6791 (2020)
  53. Effect of adiponectin on macrophage reverse cholesterol transport in adiponectin-/- mice and its mechanism. Wang Y, Wang X, Guo Y, Bian Y, Bai R, Liang B, Xiao C. Exp Ther Med 13 2757-2762 (2017)
  54. Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling. Aladin DMK, Chu YS, Shen S, Robinson RC, Dufour S, Viasnoff V, Borghi N, Thiery JP. PLoS One 16 e0260593 (2021)
  55. Functional convergence of genomic and transcriptomic architecture underlies schooling behaviour in a live-bearing fish. Corral-Lopez A, Bloch NI, van der Bijl W, Cortazar-Chinarro M, Szorkovszky A, Kotrschal A, Darolti I, Buechel SD, Romenskyy M, Kolm N, Mank JE. Nat Ecol Evol (2023)
  56. Identification of an adhesive interface for the non-clustered δ1 protocadherin-1 involved in respiratory diseases. Modak D, Sotomayor M. Commun Biol 2 354 (2019)
  57. Native adiponectin in serum binds to mammalian cells expressing T-cadherin, but not AdipoRs or calreticulin. Kita S, Fukuda S, Maeda N, Shimomura I. Elife 8 (2019)
  58. Regulation of multiple dimeric states of E-cadherin by adhesion activating antibodies revealed through Cryo-EM and X-ray crystallography. Maker A, Bolejack M, Schecterson L, Hammerson B, Abendroth J, Edwards TE, Staker B, Myler PJ, Gumbiner BM. PNAS Nexus 1 pgac163 (2022)