Adhesion GPCRs Govern Polarity of Epithelia and Cell Migration

  • David StruttEmail author
  • Ralf SchnabelEmail author
  • Franziska Fiedler
  • Simone PrömelEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 234)

Graphical Abstract


In multicellular organisms cells spatially arrange in a highly coordinated manner to form tissues and organs, which is essential for the function of an organism. The component cells and resulting structures are often polarised in one or more axes, and how such polarity is established and maintained correctly has been one of the major biological questions for many decades. Research progress has shown that many adhesion GPCRs (aGPCRs) are involved in several types of polarity. Members of the two evolutionarily oldest groups, Flamingo/Celsr and Latrophilins, are key molecules in planar cell polarity of epithelia or the propagation of cellular polarity in the early embryo, respectively. Other adhesion GPCRs play essential roles in cell migration, indicating that this receptor class includes essential molecules for the control of various levels of cellular organisation.


Planar Polarity Planar Cell Polarity Spindle Orientation Collective Cell Migration Junctional Localisation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Work in the Strutt laboratory is funded by a Wellcome Trust Senior Fellowship in Basic Biomedical Science. Work in the Prömel laboratory is funded by grants from the Deutsche Forschungsgemeinschaft (PR1534 1-1; FOR2149 Project 2 [PR 1534/2-1]) and the Medical Faculty of the University of Leipzig (Formel 1 junior research grant).


  1. 1.
    Wolpert L (2013) Cell polarity. Philos Trans R Soc Lond B Biol Sci 368:20130419PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Hunter MV, Fernandez-Gonzalez R (2013) Gastrulation: cell polarity comes full circle. Curr Biol 23:R845–R848PubMedCrossRefGoogle Scholar
  3. 3.
    Zallen JA (2007) Planar polarity and tissue morphogenesis. Cell 129:1051–1063PubMedCrossRefGoogle Scholar
  4. 4.
    Devenport D (2014) The cell biology of planar cell polarity. J Cell Biol 207:171–179PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Gubb D, Garcia-Bellido A (1982) A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. J Embryol Exp Morphol 68:37–57PubMedGoogle Scholar
  6. 6.
    Wong LL, Adler PN (1993) Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J Cell Biol 123:209–221PubMedCrossRefGoogle Scholar
  7. 7.
    Yates LL, Schnatwinkel C, Murdoch JN, Bogani D, Formstone CJ et al (2010) The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis. Hum Mol Genet 19:2251–2267PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Segalen M, Bellaiche Y (2009) Cell division orientation and planar cell polarity pathways. Semin Cell Dev Biol 20:972–977PubMedCrossRefGoogle Scholar
  9. 9.
    Li X, Roszko I, Sepich DS, Ni M, Hamm HE, Marlow FL, Solnica-Krezel L (2013) Gpr125 modulates dishevelled distribution and planar cell polarity signaling. Development 140:3028–3039PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Maduro MF (2010) Cell fate specification in the C. elegans embryo. Dev Dyn 239:1315–1329PubMedGoogle Scholar
  11. 11.
    Schnabel R, Priess JR (1997) Specification of cell fates in the early embryo. In: Riddle DL, Blumenthal T, Meyer BJ, Priess JR (eds) C. elegans II, 2nd edn. Cold Spring Harbor, New York, NYGoogle Scholar
  12. 12.
    Sulston JE, Schierenberg E, White JG, Thomson JN (1983) The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100:64–119PubMedCrossRefGoogle Scholar
  13. 13.
    Priess JR, Thomson JN (1987) Cellular interactions in early C. elegans embryos. Cell 48:241–250PubMedCrossRefGoogle Scholar
  14. 14.
    Schierenberg E (1987) Reversal of cellular polarity and early cell-cell interaction in the embryos of Caenorhabditis elegans. Dev Biol 122:452–463PubMedCrossRefGoogle Scholar
  15. 15.
    Gonczy P, Rose LS (2005) Asymmetric cell division and axis formation in the embryo. WormBook October:1–20CrossRefGoogle Scholar
  16. 16.
    Kaletta T, Schnabel H, Schnabel R (1997) Binary specification of the embryonic lineage in Caenorhabditis elegans. Nature 390:294–298PubMedCrossRefGoogle Scholar
  17. 17.
    Lin R, Hill RJ, Priess JR (1998) POP-1 and anterior-posterior fate decisions in C. elegans embryos. Cell 92:229–239PubMedCrossRefGoogle Scholar
  18. 18.
    Rocheleau CE, Downs WD, Lin R, Wittmann C, Bei Y et al (1997) Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 90:707–716PubMedCrossRefGoogle Scholar
  19. 19.
    Thorpe CJ, Schlesinger A, Carter JC, Bowerman B (1997) Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm. Cell 90:695–705PubMedCrossRefGoogle Scholar
  20. 20.
    Walston T, Tuskey C, Edgar L, Hawkins N, Ellis G et al (2004) Multiple Wnt signaling pathways converge to orient the mitotic spindle in early C. elegans embryos. Dev Cell 7:831–841PubMedCrossRefGoogle Scholar
  21. 21.
    Nance J, Zallen JA (2011) Elaborating polarity: PAR proteins and the cytoskeleton. Development 138:799–809PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Hutter H, Schnabel R (1995) Establishment of left-right asymmetry in the Caenorhabditis elegans embryo: a multistep process involving a series of inductive events. Development 121:3417–3424PubMedGoogle Scholar
  23. 23.
    Cabello J, Neukomm LJ, Gunesdogan U, Burkart K, Charette SJ et al (2010) The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac. PLoS Biol 8, e1000297PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Langenhan T, Prömel S, Mestek L, Esmaeili B, Waller-Evans H et al (2009) Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo. Dev Cell 17:494–504PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Sudhof TC (2001) alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins. Annu Rev Neurosci 24:933–962PubMedCrossRefGoogle Scholar
  26. 26.
    Willson J, Amliwala K, Davis A, Cook A, Cuttle MF et al (2004) Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans. Curr Biol 14:1374–1379PubMedCrossRefGoogle Scholar
  27. 27.
    Krasnoperov VG, Beavis R, Chepurny OG, Little AR, Plotnikov AN et al (1996) The calcium-independent receptor of alpha-latrotoxin is not a neurexin. Biochem Biophys Res Commun 227:868–875PubMedCrossRefGoogle Scholar
  28. 28.
    Krasnoperov VG, Bittner MA, Beavis R, Kuang Y, Salnikow KV et al (1997) alpha-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 18:925–937PubMedCrossRefGoogle Scholar
  29. 29.
    Müller A, Winkler J, Fiedler F, Sastradihardja T, Binder C et al (2015) Oriented cell division in the C. elegans embryo is coordinated by G-protein signaling dependent on the adhesion GPCR LAT-1. PLoS Genet 11, e1005624PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Bischoff M, Schnabel R (2006) A posterior centre establishes and maintains polarity of the Caenorhabditis elegans embryo by a Wnt-dependent relay mechanism. PLoS Biol 4, e396PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Hyman AA, White JG (1987) Determination of cell division axes in the early embryogenesis of Caenorhabditis elegans. J Cell Biol 105:2123–2135PubMedCrossRefGoogle Scholar
  32. 32.
    Boucard AA, Ko J, Sudhof TC (2012) High-affinity neurexin binding to the cell-adhesion G-protein coupled receptor CIRL1/latrophilin-1 produces an intercellular adhesion complex. J Biol Chem 287(12):9399–9413PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    O‘Sullivan ML, de Wit J, Savas JN, Comoletti D, Otto-Hitt S et al (2012) FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development. Neuron 73:903–910PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Silva JP, Lelianova VG, Ermolyuk YS, Vysokov N, Hitchen PG et al (2011) Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities. Proc Natl Acad Sci U S A 108:12113–12118PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Prömel S, Frickenhaus M, Hughes S, Mestek L, Staunton D et al (2012) The GPS motif is a molecular switch for bimodal activities of adhesion class G protein-coupled receptors. Cell Rep 2:321–331PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Demberg LM, Rothemund S, Schoneberg T, Liebscher I (2015) Identification of the tethered peptide agonist of the adhesion G protein-coupled receptor GPR64/ADGRG2. Biochem Biophys Res Commun 464(3):743–747PubMedCrossRefGoogle Scholar
  37. 37.
    Liebscher I, Schon J, Petersen SC, Fischer L, Auerbach N et al (2014) A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133. Cell Rep 9:2018–2026PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Stoveken HM, Hajduczok AG, Xu L, Tall GG (2015) Adhesion G protein-coupled receptors are activated by exposure of a cryptic tethered agonist. Proc Natl Acad Sci U S A 112:6194–6199PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Liebscher I, Schöneberg T (2016) Tethered agonism: a common activation mechanism of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  40. 40.
    Kishore A, Hall RA (2016) Versatile signaling activity of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  41. 41.
    Chae J, Kim MJ, Goo JH, Collier S, Gubb D et al (1999) The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family. Development 126:5421–5429PubMedGoogle Scholar
  42. 42.
    Usui T, Shima Y, Shimada Y, Hirano S, Burgess RW et al (1999) Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98:585–595PubMedCrossRefGoogle Scholar
  43. 43.
    Hale R, Strutt D (2015) Conservation of planar polarity pathway function across the animal kingdom. Annu Rev Genet 49:529–551PubMedCrossRefGoogle Scholar
  44. 44.
    Nordström KJ, Lagerström MC, Wallér LM, Fredriksson R, Schiöth HB (2009) The Secretin GPCRs descended from the family of Adhesion GPCRs. Mol Biol Evol 26:71–84PubMedCrossRefGoogle Scholar
  45. 45.
    Hadjantonakis AK, Formstone CJ, Little PF (1998) mCelsr1 is an evolutionarily conserved seven-pass transmembrane receptor and is expressed during mouse embryonic development. Mech Dev 78:91–95PubMedCrossRefGoogle Scholar
  46. 46.
    Hadjantonakis AK, Sheward WJ, Harmar AJ, de Galan L, Hoovers JM et al (1997) Celsr1, a neural-specific gene encoding an unusual seven-pass transmembrane receptor, maps to mouse chromosome 15 and human chromosome 22qter. Genomics 45:97–104PubMedCrossRefGoogle Scholar
  47. 47.
    Nakayama M, Nakajima D, Nagase T, Nomura N, Seki N et al (1998) Identification of high-molecular-weight proteins with multiple EGF-like motifs by motif-trap screening. Genomics 51:27–34PubMedCrossRefGoogle Scholar
  48. 48.
    Araç D, Sträter N, Seiradake E (2016) Understanding the structural basis of adhesion GPCR functions. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, HeidelbergGoogle Scholar
  49. 49.
    Lu B, Usui T, Uemura T, Jan L, Jan Y-N (1999) Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila. Curr Biol 9:1247–1250PubMedCrossRefGoogle Scholar
  50. 50.
    Goodrich LV, Strutt D (2011) Principles of planar polarity in animal development. Development 138:1877–1892PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Vinson CR, Adler PN (1987) Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature 329:549–551PubMedCrossRefGoogle Scholar
  52. 52.
    Vinson CR, Conover S, Adler PN (1989) A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains. Nature 338:262–264CrossRefGoogle Scholar
  53. 53.
    Strutt H, Strutt D (2009) Asymmetric localisation of planar polarity proteins: mechanisms and consequences. Semin Cell Dev Biol 20:957–963PubMedCrossRefGoogle Scholar
  54. 54.
    Kimura H, Usui T, Tsubouchi A, Uemura T (2006) Potential dual molecular interaction of the Drosophila 7-pass transmembrane cadherin Flamingo in dendritic morphogenesis. J Cell Sci 119:1118–1129PubMedCrossRefGoogle Scholar
  55. 55.
    Strutt H, Strutt D (2008) Differential stability of flamingo protein complexes underlies the establishment of planar polarity. Curr Biol 18:1555–1564PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Strutt H, Warrington SJ, Strutt D (2011) Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains. Dev Cell 20:511–525PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Strutt DI (2001) Asymmetric localization of Frizzled and the establishment of cell polarity in the Drosophila wing. Mol Cell 7:367–375PubMedCrossRefGoogle Scholar
  58. 58.
    Bastock R, Strutt H, Strutt D (2003) Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development 130:3007–3014PubMedCrossRefGoogle Scholar
  59. 59.
    Chen WS, Antic D, Matis M, Logan CY, Povelones M et al (2008) Asymmetric homotypic interactions of the atypical cadherin flamingo mediate intercellular polarity signaling. Cell 133:1093–1105PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Devenport D, Fuchs E (2008) Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol 10:1257–1268PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Axelrod JD (2001) Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. Genes Dev 15:1182–1187PubMedPubMedCentralGoogle Scholar
  62. 62.
    Shimada Y, Usui T, Yanagawa S, Takeichi M, Uemura T (2001) Asymmetric colocalization of Flamingo, a seven-pass transmembrane cadherin, and Dishevelled in planar cell polarization. Curr Biol 11:859–863PubMedCrossRefGoogle Scholar
  63. 63.
    Jenny A, Darken RS, Wilson PA, Mlodzik M (2003) Prickle and Strabismus form a functional complex to generate a correct axis during planar cell polarity signaling. EMBO J 22:4409–4420PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Das G, Jenny A, Klein TJ, Eaton S, Mlodzik M (2004) Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes. Development 131:4467–4476PubMedCrossRefGoogle Scholar
  65. 65.
    Feiguin F, Hannus M, Mlodzik M, Eaton S (2001) The ankyrin repeat protein Diego mediates Frizzled-dependent planar polarization. Dev Cell 1:93–101PubMedCrossRefGoogle Scholar
  66. 66.
    Tree DR, Ma D, Axelrod JD (2002) A three-tiered mechanism for regulation of planar cell polarity. Semin Cell Dev Biol 13:217–224PubMedCrossRefGoogle Scholar
  67. 67.
    Davies A, Formstone C, Mason I, Lewis J (2005) Planar polarity of hair cells in the chick inner ear is correlated with polarized distribution of c-flamingo-1 protein. Dev Dyn 233:998–1005PubMedCrossRefGoogle Scholar
  68. 68.
    Shi D, Komatsu K, Hirao M, Toyooka Y, Koyama H et al (2014) Celsr1 is required for the generation of polarity at multiple levels of the mouse oviduct. Development 141:4558–4568PubMedCrossRefGoogle Scholar
  69. 69.
    Vladar EK, Bayly RD, Sangoram AM, Scott MP, Axelrod JD (2012) Microtubules enable the planar cell polarity of airway cilia. Curr Biol 22:2203–2212PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Boutin C, Goffinet AM, Tissir F (2012) Celsr1-3 cadherins in PCP and brain development. Curr Top Dev Biol 101:161–183PubMedCrossRefGoogle Scholar
  71. 71.
    Formstone CJ (2010) 7TM-Cadherins: developmental roles and future challenges. Adv Exp Med Biol 706:14–36PubMedCrossRefGoogle Scholar
  72. 72.
    Curtin JA, Quint E, Tsipouri V, Arkell RM, Cattanach B et al (2003) Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr Biol 13:1129–1133PubMedCrossRefGoogle Scholar
  73. 73.
    Caddy J, Wilanowski T, Darido C, Dworkin S, Ting SB et al (2010) Epidermal wound repair is regulated by the planar cell polarity signaling pathway. Dev Cell 19:138–147PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Zou Y (2012) Does planar cell polarity signaling steer growth cones? Curr Top Dev Biol 101:141–160PubMedCrossRefGoogle Scholar
  75. 75.
    Gao FB, Kohwi M, Brenman JE, Jan LY, Jan YN (2000) Control of dendritic field formation in Drosophila: the roles of Flamingo and competition between homologous neurons. Neuron 28:91–101PubMedCrossRefGoogle Scholar
  76. 76.
    Lee RC, Clandinin TR, Lee CH, Chen PL, Meinertzhagen IA et al (2003) The protocadherin Flamingo is required for axon target selection in the Drosophila visual system. Nat Neurosci 6:557–563PubMedCrossRefGoogle Scholar
  77. 77.
    Senti KA, Usui T, Boucke K, Greber U, Uemura T et al (2003) Flamingo regulates R8 axon-axon and axon-target interactions in the Drosophila visual system. Curr Biol 13:828–832PubMedCrossRefGoogle Scholar
  78. 78.
    Carreira-Barbosa F, Kajita M, Morel V, Wada H, Okamoto H et al (2009) Flamingo regulates epiboly and convergence/extension movements through cell cohesive and signalling functions during zebrafish gastrulation. Development 136:383–392PubMedCrossRefGoogle Scholar
  79. 79.
    Witzel S, Zimyanin V, Carreira-Barbosa F, Tada M, Heisenberg CP (2006) Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane. J Cell Biol 175:791–802PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Qu Y, Huang Y, Feng J, Alvarez-Bolado G, Grove EA et al (2014) Genetic evidence that Celsr3 and Celsr2, together with Fzd3, regulate forebrain wiring in a Vangl-independent manner. Proc Natl Acad Sci U S A 111:E2996–E3004PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Shima Y, Kawaguchi SY, Kosaka K, Nakayama M, Hoshino M et al (2007) Opposing roles in neurite growth control by two seven-pass transmembrane cadherins. Nat Neurosci 10:963–969PubMedCrossRefGoogle Scholar
  82. 82.
    Devenport D, Oristian D, Heller E, Fuchs E (2011) Mitotic internalization of planar cell polarity proteins preserves tissue polarity. Nat Cell Biol 13:893–902PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Shrestha R, Little KA, Tamayo JV, Li W, Perlman DH et al (2015) Mitotic control of planar cell polarity by polo-like kinase 1. Dev Cell 33:522–534PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Vedula SRK, Ravasio A, Lim CT, Ladoux B (2013) Collective cell migration: a mechanistic perspective. Physiology (Bethesda, MD) 28:370–379Google Scholar
  85. 85.
    Ridley AJ (2015) Rho GTPase signalling in cell migration. Curr Opin Cell Biol 36:103–112PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Rørth P (2009) Collective cell migration. Annu Rev Cell Dev Biol 25:407–429PubMedCrossRefGoogle Scholar
  87. 87.
    Stacey M, Lin H-H, Gordon S, McKnight AJ (2000) LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors. Trends Biochem Sci 25:284–289PubMedCrossRefGoogle Scholar
  88. 88.
    Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH et al (2003) Cell migration: integrating signals from front to back. Science (New York, NY) 302:1704–1709CrossRefGoogle Scholar
  89. 89.
    Eichler W, Aust G, Hamann D (1994) Characterization of an early activation-dependent antigen on lymphocytes defined by the monoclonal antibody BL-Ac(F2). Scand J Immunol 39:111–115PubMedCrossRefGoogle Scholar
  90. 90.
    Yona S, Lin H-H, Dri P, Davies JQ, Hayhoe RPG et al (2008) Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function. FASEB J 22:741–751PubMedCrossRefGoogle Scholar
  91. 91.
    Leemans JC, te Velde AA, Florquin S, Bennink RJ, Kd B et al (2004) The epidermal growth factor-seven transmembrane (EGF-TM7) receptor CD97 is required for neutrophil migration and host defense. J Immunol 172:1125–1131PubMedCrossRefGoogle Scholar
  92. 92.
    Bokoch GM (2005) Regulation of innate immunity by Rho GTPases. Trends Cell Biol 15:163–171PubMedCrossRefGoogle Scholar
  93. 93.
    Galle J, Sittig D, Hanisch I, Wobus M, Wandel E et al (2006) Individual cell-based models of tumor-environment interactions: multiple effects of CD97 on tumor invasion. Am J Pathol 169:1802–1811PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Li S, Jin Z, Koirala S, Bu L, Xu L et al (2008) GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci 28:5817–5826PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Luo R, Jeong S-J, Jin Z, Strokes N, Li S et al (2011) G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proc Natl Acad Sci U S A 108:12925–12930PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Singer K, Luo R, Jeong S-J, Piao X (2013) GPR56 and the developing cerebral cortex: cells, matrix, and neuronal migration. Mol Neurobiol 47:186–196PubMedCrossRefGoogle Scholar
  97. 97.
    Piao X, Basel-Vanagaite L, Straussberg R, Grant PE, Pugh EW et al (2002) An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21. Am J Hum Genet 70:1028–1033PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Kuhnert F, Mancuso MR, Shamloo A, Wang H-T, Choksi V et al (2010) Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124. Science (New York, NY) 330:985–989CrossRefGoogle Scholar
  99. 99.
    Valtcheva N, Primorac A, Jurisic G, Hollmén M, Detmar M (2013) The orphan adhesion G protein-coupled receptor GPR97 regulates migration of lymphatic endothelial cells via the small GTPases RhoA and Cdc42. J Biol Chem 288:35736–35748PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Fredriksson R, Lagerström MC, Lundin L-G, Schiöth HB (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 63:1256–1272PubMedCrossRefGoogle Scholar
  101. 101.
    Fredriksson R, Gloriam DE, Hoglund PJ, Lagerstrom MC, Schioth HB (2003) There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem Biophys Res Commun 301:725–734PubMedCrossRefGoogle Scholar
  102. 102.
    Schioth HB, Fredriksson R (2005) The GRAFS classification system of G-protein coupled receptors in comparative perspective. Gen Comp Endocrinol 142:94–101PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Bateson Centre and Department of Biomedical ScienceUniversity of SheffieldSheffieldUK
  2. 2.Institute of Genetics, TU BraunschweigBraunschweigGermany
  3. 3.Medical FacultyInstitute of Biochemistry, Leipzig UniversityLeipzigGermany

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