Native Serotonin 5-HT2C receptors are expressed as homodimers on the apical surface of choroid plexus epithelial cells

Molecular Pharmacology

Volumn 87, Issue 4, 2015, Pages 660-673

  Herrick Davis, Katharine ^a   Grinde, Ellinor ^a   Lindsley, Tara ^a   Teitler, Milt ^a   Mancia, Filippo ^b   Cowan, Ann ^c   Mazurkiewicz, Joseph E ^a  

^a ALBANY MEDICAL COLLEGE   (United States)

^b Columbia University ^*  (United States)

^c Raymond and Beverly Sacker Laboratory of Genetics and Molecular Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; G PROTEIN COUPLED RECEPTOR; HOMODIMER; MONOMER; OLIGOMER; SEROTONIN 2A RECEPTOR; SEROTONIN 2C RECEPTOR; AFFINITY LABELING; GREEN FLUORESCENT PROTEIN; IMMUNOGLOBULIN F(AB) FRAGMENT; MONOCLONAL ANTIBODY;

ANTIGEN BINDING; ARTICLE; CELL SURFACE; CHOROID PLEXUS; EMBRYO; EPITHELIUM CELL; EXPRESSION VECTOR; FLUORESCENCE CORRELATION SPECTROSCOPY; HEK293 CELL LINE; HISTOGRAM; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; OLIGOMERIZATION; PHOTON COUNTING HISTOGRAM; PRIORITY JOURNAL; WESTERN BLOTTING; AFFINITY LABELING; ANIMAL; CELL CULTURE; GENETICS; IMMUNOLOGY; METABOLISM; PROMOTER REGION; PROTEIN MULTIMERIZATION; RADIOASSAY; SIGNAL TRANSDUCTION; SPRAGUE DAWLEY RAT;

AFFINITY LABELS; ANIMALS; ANTIBODIES, MONOCLONAL; CELLS, CULTURED; CHOROID PLEXUS; EPITHELIAL CELLS; GREEN FLUORESCENT PROTEINS; HEK293 CELLS; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; PROMOTER REGIONS, GENETIC; PROTEIN MULTIMERIZATION; RADIOLIGAND ASSAY; RATS, SPRAGUE-DAWLEY; RECEPTOR, SEROTONIN, 5-HT2C; SIGNAL TRANSDUCTION;

EID: 84981719280     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.114.096636     Document Type: Article

References (60)

1. Albizu L, Cottet M, Kralikova M, Stoev S, Seyer R, Brabet I, Roux T, Bazin H, Bourrier E, and Lamarque L et al. (2010) Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat Chem Biol 6:587-594.
2. Assur Z, Schieren I, Hendrickson WA, and Mancia F (2007) Two-color selection for amplified co-production of proteins in mammalian cells. Protein Expr Purif 55: 319-324.
3. Backstrom JR, Westphal RS, Canton H, and Sanders-Bush E (1995) Identification of rat serotonin 5-HT2C receptors as glycoproteins containing N-linked oligosaccharides. Brain Res Mol Brain Res 33:311-318.
4. Banères JL and Parello J (2003) Structure-based analysis of GPCR function: Evidence for a novel pentameric assembly between the dimeric leukotriene B4 receptor BLT1 and the G-protein. J Mol Biol 329:815-829.
5. Bayburt TH, Leitz AJ, Xie G, Oprian DD, and Sligar SG (2007) Transducin activation by nanoscale lipid bilayers containing one and two rhodopsins. J Biol Chem 282: 14875-14881.
6. Berg KA, Rowan MP, Gupta A, Sanchez TA, Silva M, Gomes I, McGuire BA, Portoghese PS, Hargreaves KM, and Devi LA et al. (2012) Allosteric interactions between d and k opioid receptors in peripheral sensory neurons. Mol Pharmacol 81: 264-272.
7. Berridge MJ, Dawson RM, Downes CP, Heslop JP, and Irvine RF (1983) Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J 212:473-482.
8. Briddon SJ, Gandía J, Amaral OB, Ferré S, Lluís C, Franco R, Hill SJ, and Ciruela F (2008) Plasma membrane diffusion of G protein-coupled receptor oligomers. Biochim Biophys Acta 1783:2262-2268.
9. Calebiro D, Rieken F, Wagner J, Sungkaworn T, Zabel U, Borzi A, Cocucci E, Zürn A, and Lohse MJ (2013) Single-molecule analysis of fluorescently labeled G-proteincoupled receptors reveals complexes with distinct dynamics and organization. Proc Natl Acad Sci USA 110:743-748.
10. Chen Y, Müller JD, So PT, and Gratton E (1999) The photon counting histogram in fluorescence fluctuation spectroscopy. Biophys J 77:553-567.
11. Cole RW, Jinadasa T, and Brown CM (2011) Measuring and interpreting point spread functions to determine confocal microscope resolution and ensure quality control. Nat Protoc 6:1929-1941.
12. Corriden R, Kilpatrick LE, Kellam B, Briddon SJ, and Hill SJ (2014) Kinetic analysis of antagonist-occupied adenosine-A3 receptors within membrane microdomains of individual cells provides evidence of receptor dimerization and allosterism. FASEB J 28:4211-4222.
13. Dickson PW, Howlett GJ, and Schreiber G (1985) Rat transthyretin (prealbumin). Molecular cloning, nucleotide sequence, and gene expression in liver and brain. J Biol Chem 260:8214-8219.
14. Elson EL (2011) Fluorescence correlation spectroscopy: past, present, future. Biophys J 101:2855-2870.
15. Esterle TM and Sanders-Bush E (1992) Serotonin agonists increase transferrin levels via activation of 5-HT1C receptors in choroid plexus epithelium. J Neurosci 12: 4775-4782.
16. Ferré S, Casadó V, Devi LA, Filizola M, Jockers R, Lohse MJ, Milligan G, Pin JP, and Guitart X (2014) G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives. Pharmacol Rev 66:413-434.
17. Fujita W, Gomes I, and Devi LA (2015) Heteromers of m-d opioid receptors: new pharmacology and novel therapeutic possibilities. Br J Pharmacol 172:375-387.
18. Ganguly S and Chattopadhyay A (2010) Cholesterol depletion mimics the effect of cytoskeletal destabilization on membrane dynamics of the serotonin1A receptor: A zFCS study. Biophys J 99:1397-1407.
19. González S, Rangel-Barajas C, Peper M, Lorenzo R, Moreno E, Ciruela F, Borycz J, Ortiz J, Lluís C, and Franco R et al. (2012) Dopamine D4 receptor, but not the ADHD- Associated D4.7 variant, forms functional heteromers with the dopamine D2S receptor in the brain. Mol Psychiatry 17:650-662.
20. Han Y, Moreira IS, Urizar E, Weinstein H, and Javitch JA (2009) Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation. Nat Chem Biol 5:688-695.
21. Hartig PR, Hoffman BJ, Kaufman MJ, and Hirata F (1990) The 5-HT1C receptor. Ann N Y Acad Sci 600:149-166, discussion 166-167.
22. Hasbi A, O'Dowd BF, and George SR (2011) Dopamine D1-D2 receptor heteromer signaling pathway in the brain: Emerging physiological relevance. Mol Brain 4:26.
23. Hegener O, Prenner L, Runkel F, Baader SL, Kappler J, and Häberlein H (2004) Dynamics of beta2- Adrenergic receptor-ligand complexes on living cells. Biochemistry 43:6190-6199.
24. Herrick-Davis K (2013) Functional significance of serotonin receptor dimerization. Exp Brain Res 230:375-386.
25. Herrick-Davis K, Grinde E, Cowan A, and Mazurkiewicz JE (2013) Fluorescence correlation spectroscopy analysis of serotonin, adrenergic, muscarinic, and dopamine receptor dimerization: The oligomer number puzzle. Mol Pharmacol 84:630-642.
26. Herrick-Davis K, Grinde E, Lindsley T, Cowan A, and Mazurkiewicz JE (2012) Oligomer size of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor revealed by fluorescence correlation spectroscopy with photon counting histogram analysis: Evidence for homodimers without monomers or tetramers. J Biol Chem 287: 23604-23614.
27. Herrick-Davis K, Grinde E, and Mazurkiewicz JE (2004) Biochemical and biophysical characterization of serotonin 5-HT2C receptor homodimers on the plasma membrane of living cells. Biochemistry 43:13963-13971.
28. Herrick-Davis K, Grinde E, and Niswender CM (1999) Serotonin 5-HT2C receptor RNA editing alters receptor basal activity: implications for serotonergic signal transduction. J Neurochem 73:1711-1717.
29. Herrick-Davis K and Mazurkiewicz JE (2013) Fluorescence correlation spectroscopy and photon-counting histogram analysis of receptor-receptor interactions. Methods Cell Biol 117:181-196.
30. Herrick-Davis K, Weaver BA, Grinde E, and Mazurkiewicz JE (2006) Serotonin 5-HT2C receptor homodimer biogenesis in the endoplasmic reticulum: Real- Time visualization with confocal fluorescence resonance energy transfer. J Biol Chem 281:27109-27116.
31. Jastrzebska B, Orban T, Golczak M, Engel A, and Palczewski K (2013a) Asymmetry of the rhodopsin dimer in complex with transducin. FASEB J 27:1572-1584.
32. Jastrzebska B, Ringler P, Palczewski K, and Engel A (2013b) The rhodopsintransducin complex houses two distinct rhodopsin molecules. J Struct Biol 182: 164-172.
33. Kasai RS and Kusumi A (2014) Single-molecule imaging revealed dynamic GPCR dimerization. Curr Opin Cell Biol 27:78-86.
34. Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, and Bickerdike M (2004) Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol 370:114-123.
35. Kuang YQ, Charette N, Frazer J, Holland PJ, Attwood KM, Dellaire G, and Dupré DJ (2012) Dopamine receptor-interacting protein 78 acts as a molecular chaperone for CCR5 chemokine receptor signaling complex organization. PLoS ONE 7:e40522.
36. Liang Y, Fotiadis D, Filipek S, Saperstein DA, Palczewski K, and Engel A (2003) Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. J Biol Chem 278:21655-21662.
37. Malengo G, Andolfo A, Sidenius N, Gratton E, Zamai M, and Caiolfa VR (2008) Fluorescence correlation spectroscopy and photon counting histogram on membrane proteins: functional dynamics of the glycosylphosphatidylinositol- Anchored urokinase plasminogen activator receptor. J Biomed Opt 13:031215.
38. Mancia F, Brenner-Morton S, Siegel R, Assur Z, Sun Y, Schieren I, Mendelsohn M, Axel R, and Hendrickson WA (2007) Production and characterization of monoclonal antibodies sensitive to conformation in the 5HT2c serotonin receptor. Proc Natl Acad Sci USA 104:4303-4308.
39. Maurice P, Kamal M, and Jockers R (2011) Asymmetry of GPCR oligomers supports their functional relevance. Trends Pharmacol Sci 32:514-520.
40. Milligan G (2013) The prevalence, maintenance, and relevance of G protein-coupled receptor oligomerization. Mol Pharmacol 84:158-169.
41. Müller JD, Chen Y, and Gratton E (2000) Resolving heterogeneity on the single molecular level with the photon-counting histogram. Biophys J 78:474-486.
42. Newman-Tancredi A, Cussac D, Quentric Y, Touzard M, Verrièle L, Carpentier N, and Millan MJ (2002) Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes. J Pharmacol Exp Ther 303: 815-822.
43. Pellissier LP, Barthet G, Gaven F, Cassier E, Trinquet E, Pin JP, Marin P, Dumuis A, Bockaert J, and Banères JL et al. (2011) G protein activation by serotonin type 4 receptor dimers: Evidence that turning on two protomers is more efficient. J Biol Chem 286:9985-9997.
44. Pin JP, Comps-Agrar L, Maurel D, Monnier C, Rives ML, Trinquet E, Kniazeff J, Rondard P, and Prézeau L (2009) G-protein-coupled receptor oligomers: Two or more for what? Lessons from mGlu and GABAB receptors. J Physiol 587:5337-5344.
45. Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, and Calinski D et al. (2011) Crystal structure of the b2 adrenergic receptor-Gs protein complex. Nature 477:549-555.
46. Rivero-Müller A, Chou YY, Ji I, Lajic S, Hanyaloglu AC, Jonas K, Rahman N, Ji TH, and Huhtaniemi I (2010) Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation. Proc Natl Acad Sci USA 107:2319-2324.
47. Salahpour A, Angers S, Mercier JF, Lagacé M, Marullo S, and Bouvier M (2004) Homodimerization of the beta2- Adrenergic receptor as a prerequisite for cell surface targeting. J Biol Chem 279:33390-33397.
48. Saltzman AG, Morse B, Whitman MM, Ivanshchenko Y, Jaye M, and Felder S (1991) Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes. Biochem Biophys Res Commun 181:1469-1478.
49. Skerra A (1994) A general vector, pASK84, for cloning, bacterial production, and single-step purification of antibody Fab fragments. Gene 141:79-84.
50. Smith C, Toohey N, Knight JA, Klein MT, and Teitler M (2011) Risperidoneinduced inactivation and clozapine-induced reactivation of rat cortical astrocyte 5-hydroxytryptamine7 receptors: Evidence for in situ G protein-coupled receptor homodimer protomer cross- Talk. Mol Pharmacol 79:318-325.
51. Teichmann A, Gibert A, Lampe A, Grzesik P, Rutz C, Furkert J, Schmoranzer J, Krause G, Wiesner B, and Schülein R (2014) The specific monomer/dimer equilibrium of the corticotropin-releasing factor receptor type 1 is established in the endoplasmic reticulum. J Biol Chem 289:24250-24262.
52. Teitler M and Klein MT (2012) A new approach for studying GPCR dimers: druginduced inactivation and reactivation to reveal GPCR dimer function in vitro, in primary culture, and in vivo. Pharmacol Ther 133:205-217.
53. Ulbrich MH and Isacoff EY (2007) Subunit counting in membrane-bound proteins. Nat Methods 4:319-321.
54. Villalobos AR, Parmelee JT, and Pritchard JB (1997) Functional characterization of choroid plexus epithelial cells in primary culture. J Pharmacol Exp Ther 282: 1109-1116.
55. Wacker D, Wang C, Katritch V, Han GW, Huang XP, Vardy E, McCorvy JD, Jiang Y, Chu M, and Siu FY et al. (2013) Structural features for functional selectivity at serotonin receptors. Science 340:615-619.
56. Waldhoer M, Fong J, Jones RM, Lunzer MM, Sharma SK, Kostenis E, Portoghese PS, and Whistler JL (2005) A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers. Proc Natl Acad Sci USA 102:9050-9055.
57. Whorton MR, Bokoch MP, Rasmussen SG, Huang B, Zare RN, Kobilka B, and Sunahara RK (2007) A monomeric G protein-coupled receptor isolated in a highdensity lipoprotein particle efficiently activates its G protein. Proc Natl Acad Sci USA 104:7682-7687.
58. Youker RT, Bruns JR, Costa SA, Rbaibi Y, Lanni F, Kashlan OB, Teng H, and Weisz OA (2013) Multiple motifs regulate apical sorting of p75 via a mechanism that involves dimerization and higher-order oligomerization. Mol Biol Cell 24: 1996-2007.
59. Zacharias DA, Violin JD, Newton AC, and Tsien RY (2002) Partitioning of lipidmodified monomeric GFPs into membrane microdomains of live cells. Science 296: 913-916.
60. Zoenen M, Urizar E, Swillens S, Vassart G, and Costagliola S (2012) Evidence for activity-regulated hormone-binding cooperativity across glycoprotein hormone receptor homomers. Nat Commun 3:1007-1017.