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Pierce KL, Premont RT, Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3(9):639–650
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(3):725–734
Langenhan T, Aust G, Hamann J (2013) Sticky signaling–adhesion class G protein-coupled receptors take the stage. Sci Signal 6(276):re3
Hamann J, Aust G, Arac D, Engel FB, Formstone C, Fredriksson R et al (2015) International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev 67(2):338–367
Krishnan A, Nijmeijer S, de Graaf C, Schiöth HB (2016) Classification, nomenclature and structural aspects of adhesion GPCRs. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg
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, Heidelberg
Krasnoperov VG, Bittner MA, Beavis R, Kuang Y, Salnikow KV, Chepurny OG et al (1997) alpha-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 18(6):925–937
Lin HH, Chang GW, Davies JQ, Stacey M, Harris J, Gordon S (2004) Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif. J Biol Chem 279(30):31823–31832
Nieberler M, Kittel RJ, Petrenko AG, Lin H-H, Langenhan T (2016) Control of adhesion GPCR function through proteolytic processing. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg
Arac D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Sudhof TC et al (2012) A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis. EMBO J 31(6):1364–1378
Liebscher I, Ackley B, Arac D, Ariestanti DM, Aust G, Bae BI et al (2014) New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors. Ann N Y Acad Sci 1333:43–64
Promel S, Langenhan T, Arac D (2013) Matching structure with function: the GAIN domain of adhesion-GPCR and PKD1-like proteins. Trends Pharmacol Sci 34(8):470–478
Davletov BA, Shamotienko OG, Lelianova VG, Grishin EV, Ushkaryov YA (1996) Isolation and biochemical characterization of a Ca2+-independent alpha-latrotoxin-binding protein. J Biol Chem 271(38):23239–23245
Lelianova VG, Davletov BA, Sterling A, Rahman MA, Grishin EV, Totty NF et al (1997) Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J Biol Chem 272(34):21504–21508
Ichtchenko K, Khvotchev M, Kiyatkin N, Simpson L, Sugita S, Sudhof TC (1998) alpha-Latrotoxin action probed with recombinant toxin: receptors recruit alpha-latrotoxin but do not transduce an exocytotic signal. EMBO J 17(21):6188–6199
Volynski KE, Silva JP, Lelianova VG, Atiqur Rahman M, Hopkins C, Ushkaryov YA (2004) Latrophilin fragments behave as independent proteins that associate and signal on binding of LTX(N4C). EMBO J 23(22):4423–4433
Rahman MA, Ashton AC, Meunier FA, Davletov BA, Dolly JO, Ushkaryov YA (1999) Norepinephrine exocytosis stimulated by alpha-latrotoxin requires both external and stored Ca2+ and is mediated by latrophilin, G proteins and phospholipase C. Philos Trans R Soc Lond B Biol Sci 354(1381):379–386
Piao X, Hill RS, Bodell A, Chang BS, Basel-Vanagaite L, Straussberg R et al (2004) G protein-coupled receptor-dependent development of human frontal cortex. Science 303(5666):2033–2036
Bae BI, Tietjen I, Atabay KD, Evrony GD, Johnson MB, Asare E et al (2014) Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science 343(6172):764–768
Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H (2008) Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. J Biol Chem 283(21):14469–14478
Paavola KJ, Stephenson JR, Ritter SL, Alter SP, Hall RA (2011) The N terminus of the adhesion G protein-coupled receptor GPR56 controls receptor signaling activity. J Biol Chem 286(33):28914–28921
Shashidhar S, Lorente G, Nagavarapu U, Nelson A, Kuo J, Cummins J et al (2005) GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion. Oncogene 24(10):1673–1682
Wu MP, Doyle JR, Barry B, Beauvais A, Rozkalne A, Piao X et al (2013) G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle development in vivo. FEBS J 280(23):6097–6113
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(19):6194–6199
Kim JE, Han JM, Park CR, Shin KJ, Ahn C, Seong JY et al (2010) Splicing variants of the orphan G-protein-coupled receptor GPR56 regulate the activity of transcription factors associated with tumorigenesis. J Cancer Res Clin Oncol 136(1):47–53
Kishore A, Purcell RH, Nassiri-Toosi Z, Hall RA (2016) Stalk-dependent and stalk-independent signaling by the adhesion G protein-coupled receptors GPR56 (ADGRG1) and BAI1 (ADGRB1). J Biol Chem 291(7):3385–3394
Yang L, Chen G, Mohanty S, Scott G, Fazal F, Rahman A et al (2011) GPR56 regulates VEGF production and angiogenesis during melanoma progression. Cancer Res 71(16):5558–5568
Little KD, Hemler ME, Stipp CS (2004) Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell 15(5):2375–2387
Ohta S, Sakaguchi S, Kobayashi Y, Mizuno N, Tago K, Itoh H (2015) Agonistic antibodies reveal the function of GPR56 in human glioma U87-MG cells. Biol Pharm Bull 38(4):594–600
Peeters MC, Fokkelman M, Boogaard B, Egerod KL, van de Water B, IJzerman AP et al (2015) The adhesion G protein-coupled receptor G2 (ADGRG2/GPR64) constitutively activates SRE and NFkB and is involved in cell adhesion and migration. Cell Signal 27(12):2579–2588
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):743–747
Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X (2012) Signaling property study of adhesion G-protein-coupled receptors. FEBS Lett 586(8):1214–1219
Wilde C, Fischer L, Lede V, Kirchberger J, Rothemund S, Schoneberg T et al (2016) The constitutive activity of the adhesion GPCR GPR114/ADGRG5 is mediated by its tethered agonist. FASEB J 30(2):666–673
Monk KR, Naylor SG, Glenn TD, Mercurio S, Perlin JR, Dominguez C et al (2009) A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Science 325(5946):1402–1405
Paavola KJ, Sidik H, Zuchero JB, Eckart M, Talbot WS (2014) Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126. Sci Signal 7(338):ra76
Mogha A, Benesh AE, Patra C, Engel FB, Schoneberg T, Liebscher I et al (2013) Gpr126 functions in Schwann cells to control differentiation and myelination via G-protein activation. J Neurosci 33(46):17976–17985
Liebscher I, Schon J, Petersen SC, Fischer L, Auerbach N, Demberg LM et al (2014) A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133. Cell Rep 9(6):2018–2026
Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z et al (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450(7168):430–434
Das S, Sarkar A, Ryan KA, Fox S, Berger AH, Juncadella IJ et al (2014) Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells. FASEB J 28(5):2214–2224
Mazaheri F, Breus O, Durdu S, Haas P, Wittbrodt J, Gilmour D et al (2014) Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia. Nat Commun 5:4046
Das S, Owen KA, Ly KT, Park D, Black SG, Wilson JM et al (2011) Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria. Proc Natl Acad Sci U S A 108(5):2136–2141
Hochreiter-Hufford AE, Lee CS, Kinchen JM, Sokolowski JD, Arandjelovic S, Call JA et al (2013) Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature 497(7448):263–267
Duman JG, Tzeng CP, Tu YK, Munjal T, Schwechter B, Ho TS et al (2013) The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites. J Neurosci 33(16):6964–6978
Zhu D, Li C, Swanson AM, Villalba RM, Guo J, Zhang Z et al (2015) BAI1 regulates spatial learning and synaptic plasticity in the hippocampus. J Clin Invest 125(4):1497–1508
Stephenson JR, Paavola KJ, Schaefer SA, Kaur B, Van Meir EG, Hall RA (2013) Brain-specific angiogenesis inhibitor-1 signaling, regulation, and enrichment in the postsynaptic density. J Biol Chem 288(31):22248–22256
Okajima D, Kudo G, Yokota H (2010) Brain-specific angiogenesis inhibitor 2 (BAI2) may be activated by proteolytic processing. J Recept Signal Transduct Res 30(3):143–153
Ward Y, Lake R, Yin JJ, Heger CD, Raffeld M, Goldsmith PK et al (2011) LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells. Cancer Res 71(23):7301–7311
Hu QX, Dong JH, Du HB, Zhang DL, Ren HZ, Ma ML et al (2014) Constitutive Galphai coupling activity of very large G protein-coupled receptor 1 (VLGR1) and its regulation by PDZD7 protein. J Biol Chem 289(35):24215–24225
Bohnekamp J, Schoneberg T (2011) Cell adhesion receptor GPR133 couples to Gs protein. J Biol Chem 286(49):41912–41916
Silva JP, Lelianova VG, Ermolyuk YS, Vysokov N, Hitchen PG, Berninghausen O 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(29):12113–12118
Tobaben S, Sudhof TC, Stahl B (2002) Genetic analysis of alpha-latrotoxin receptors reveals functional interdependence of CIRL/latrophilin 1 and neurexin 1 alpha. J Biol Chem 277(8):6359–6365
O’Sullivan ML, de Wit J, Savas JN, Comoletti D, Otto-Hitt S, Yates JR III et al (2012) FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development. Neuron 73(5):903–910
Jackson VA, del Toro D, Carrasquero M, Roversi P, Harlos K, Klein R et al (2015) Structural basis of latrophilin-FLRT interaction. Structure 23(4):774–781
Huang YS, Chiang NY, Hu CH, Hsiao CC, Cheng KF, Tsai WP et al (2012) Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol Cell Biol 32(8):1408–1420
Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J et al (2003) The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood 102(8):2916–2924
Karpus ON, Veninga H, Hoek RM, Flierman D, van Buul JD, Vandenakker CC et al (2013) Shear stress-dependent downregulation of the adhesion-G protein-coupled receptor CD97 on circulating leukocytes upon contact with its ligand CD55. J Immunol 190(7):3740–3748
Wang T, Ward Y, Tian L, Lake R, Guedez L, Stetler-Stevenson WG et al (2005) CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. Blood 105(7):2836–2844
Wandel E, Saalbach A, Sittig D, Gebhardt C, Aust G (2012) Thy-1 (CD90) is an interacting partner for CD97 on activated endothelial cells. J Immunol 188(3):1442–1450
Sigoillot SM, Iyer K, Binda F, Gonzalez-Calvo I, Talleur M, Vodjdani G et al (2015) The secreted protein C1QL1 and its receptor BAI3 control the synaptic connectivity of excitatory inputs converging on cerebellar Purkinje cells. Cell Rep 10(5):820–832
Bolliger MF, Martinelli DC, Sudhof TC (2011) The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins. Proc Natl Acad Sci U S A 108(6):2534–2539
Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X (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(31):12925–12930
Petersen SC, Luo R, Liebscher I, Giera S, Jeong SJ, Mogha A et al (2015) The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with laminin-211. Neuron 85(4):755–769
Xu L, Hynes RO (2007) GPR56 and TG2: possible roles in suppression of tumor growth by the microenvironment. Cell Cycle 6(2):160–165
Boucard AA, Maxeiner S, Sudhof TC (2014) Latrophilins function as heterophilic cell-adhesion molecules by binding to teneurins: regulation by alternative splicing. J Biol Chem 289(1):387–402
Bang ML, Owczarek S (2013) A matter of balance: role of neurexin and neuroligin at the synapse. Neurochem Res 38(6):1174–1189
Geppert M, Khvotchev M, Krasnoperov V, Goda Y, Missler M, Hammer RE et al (1998) Neurexin I alpha is a major alpha-latrotoxin receptor that cooperates in alpha-latrotoxin action. J Biol Chem 273(3):1705–1710
Boucard AA, Ko J, Sudhof TC (2012) High affinity neurexin binding to cell adhesion G-protein-coupled receptor CIRL1/latrophilin-1 produces an intercellular adhesion complex. J Biol Chem 287(12):9399–9413
Hamann J, Vogel B, van Schijndel GM, van Lier RA (1996) The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J Exp Med 184(3):1185–1189
Hamann J, Stortelers C, Kiss-Toth E, Vogel B, Eichler W, van Lier RA (1998) Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane receptor CD97. Eur J Immunol 28(5):1701–1707
Lin HH, Stacey M, Saxby C, Knott V, Chaudhry Y, Evans D et al (2001) Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions: dissection of the CD97-CD55 complex. J Biol Chem 276(26):24160–24169
Iijima T, Miura E, Watanabe M, Yuzaki M (2010) Distinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins. Eur J Neurosci 31(9):1606–1615
Kakegawa W, Mitakidis N, Miura E, Abe M, Matsuda K, Takeo YH et al (2015) Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum. Neuron 85(2):316–329
Xu L, Begum S, Hearn JD, Hynes RO (2006) GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc Natl Acad Sci U S A 103(24):9023–9028
Yang L, Friedland S, Corson N, Xu L (2014) GPR56 inhibits melanoma growth by internalizing and degrading its ligand TG2. Cancer Res 74(4):1022–1031
Singer K, Luo R, Jeong SJ, Piao X (2013) GPR56 and the developing cerebral cortex: cells, matrix, and neuronal migration. Mol Neurobiol 47(1):186–196
Luo R, Jin Z, Deng Y, Strokes N, Piao X (2012) Disease-associated mutations prevent GPR56-collagen III interaction. PLoS One 7(1), e29818
Chiang NY, Hsiao CC, Huang YS, Chen HY, Hsieh IJ, Chang GW et al (2011) Disease-associated GPR56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. J Biol Chem 286(16):14215–14225
Jin Z, Tietjen I, Bu L, Liu-Yesucevitz L, Gaur SK, Walsh CA et al (2007) Disease-associated mutations affect GPR56 protein trafficking and cell surface expression. Hum Mol Genet 16(16):1972–1985
Weston MD, Luijendijk MW, Humphrey KD, Moller C, Kimberling WJ (2004) Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II. Am J Hum Genet 74(2):357–366
Robinson A, Escuin S, Doudney K, Vekemans M, Stevenson RE, Greene ND et al (2012) Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. Hum Mutat 33(2):440–447
Paavola KJ, Hall RA (2012) Adhesion G protein-coupled receptors: signaling, pharmacology, and mechanisms of activation. Mol Pharmacol 82(5):777–783
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, Heidelberg
Coughlin SR (2000) Thrombin signalling and protease-activated receptors. Nature 407(6801):258–264
Promel S, Waller-Evans H, Dixon J, Zahn D, Colledge WH, Doran J et al (2012) Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse. Dev Dyn 241(10):1591–1602
Promel S, Frickenhaus M, Hughes S, Mestek L, Staunton D, Woollard A et al (2012) The GPS motif is a molecular switch for bimodal activities of adhesion class G protein-coupled receptors. Cell Rep 2(2):321–331
Krasnoperov V, Deyev IE, Serova OV, Xu C, Lu Y, Buryanovsky L et al (2009) Dissociation of the subunits of the calcium-independent receptor of alpha-latrotoxin as a result of two-step proteolysis. Biochemistry 48(14):3230–3238
Scholz N, Gehring J, Guan C, Ljaschenko D, Fischer R, Lakshmanan V et al (2015) The adhesion GPCR latrophilin/CIRL shapes mechanosensation. Cell Rep 11(6):866–874
Scholz N, Monk KR, Kittel RJ, Langenhan T (2016) Adhesion GPCRs as a putative class of metabotropic mechanosensors. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg
Knapp B, Wolfrum U (2016) Adhesion G protein-coupled receptor-related protein networks. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Springer, Heidelberg
Zou J, Zheng T, Ren C, Askew C, Liu XP, Pan B et al (2014) Deletion of PDZD7 disrupts the Usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice. Hum Mol Genet 23(9):2374–2390
Lanoue V, Usardi A, Sigoillot SM, Talleur M, Iyer K, Mariani J et al (2013) The adhesion-GPCR BAI3, a gene linked to psychiatric disorders, regulates dendrite morphogenesis in neurons. Mol Psychiatry 18(8):943–950
Jeong BC, Kim MY, Lee JH, Kee HJ, Kho DH, Han KE et al (2006) Brain-specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as a transcriptional repressor. FEBS Lett 580(2):669–676
Nishimura T, Honda H, Takeichi M (2012) Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell 149(5):1084–1097
Li X, Roszko I, Sepich DS, Ni M, Hamm HE, Marlow FL et al (2013) Gpr125 modulates Dishevelled distribution and planar cell polarity signaling. Development 140(14):3028–3039
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The authors’ research is supported by the National Institutes of Health.
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Kishore, A., Hall, R.A. (2016). Versatile Signaling Activity of Adhesion GPCRs. In: Langenhan, T., Schöneberg, T. (eds) Adhesion G Protein-coupled Receptors. Handbook of Experimental Pharmacology, vol 234. Springer, Cham. https://doi.org/10.1007/978-3-319-41523-9_7
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