Rare human nicotinic acetylcholine receptor α4 subunit (CHRNA4) variants affect expression and function of high-affinity nicotinic acetylcholine receptorss

Journal of Pharmacology and Experimental Therapeutics

Volumn 348, Issue 3, 2014, Pages 410-420

  McClure Begley, T D ^a,b   Papke, R L ^c   Stone, K L ^d   Stokes, C ^c   Levy, A D ^a,e   Gelernter, J ^a,f,h   Xie, P ^e,h   Lindstrom, J ⁱ   Picciotto, M R ^a,d,g  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF FLORIDA   (United States)

^d W M Keck Biotechnology Research Laboratory   (United States)

^e Interdepartmental Neuroscience Program   (United States)

^f Department of Genetics ^*  (United States)

^g VA CONNECTICUT HEALTHCARE SYSTEM   (United States)

^h DUKE UNIVERSITY   (United States)

ⁱ UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NICOTINE; NICOTINIC AGENT; NICOTINIC RECEPTOR ALPHA4;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ARTICLE; CELL STRAIN HEK293; CELLULAR DISTRIBUTION; CHRNA4 GENE; CONTROLLED STUDY; DRUG RECEPTOR BINDING; GENETIC VARIABILITY; HUMAN; HUMAN CELL; LIQUID CHROMATOGRAPHY; NONHUMAN; OOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEOMICS; RECEPTOR UPREGULATION; TANDEM MASS SPECTROMETRY; VOLTAGE CLAMP TECHNIQUE; XENOPUS LAEVIS;

ANIMALS; BICYCLO COMPOUNDS, HETEROCYCLIC; CELL MEMBRANE; FEMALE; HEK293 CELLS; HUMANS; NICOTINE; NICOTINIC AGONISTS; OOCYTES; PHOSPHORYLATION; POLYMORPHISM, GENETIC; PROTEIN SUBUNITS; PYRIDINES; RECEPTORS, NICOTINIC; UP-REGULATION; XENOPUS LAEVIS;

EID: 84896730315     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.113.209767     Document Type: Article

References (50)

1. Bierut LJ, Stitzel JA, Wang JC, Hinrichs AL, Grucza RA, Xuei X, Saccone NL, Saccone SF, Bertelsen S, and Fox L, et al. (2008) Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry 165:1163-1171.
2. Benowitz NL (1996) Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol 36:597-613.
3. Gotti C, Moretti M, Meinerz NM, Clementi F, Gaimarri A, Collins AC, and Marks MJ (2008) Partial deletion of the nicotinic cholinergic receptor alpha 4 or beta 2 subunit genes changes the acetylcholine sensitivity of receptor-mediated 86Rb1 efflux in cortex and thalamus and alters relative expression of alpha 4 and beta 2 subunits. Mol Pharmacol 73:1796-1807.
4. Han S, Gelernter J, Luo X, and Yang BZ (2010) Meta-analysis of 15 genome-wide linkage scans of smoking behavior. Biol Psychiatry 67:12-19.
5. Han S, Yang BZ, Kranzler HR, Oslin D, Anton R, and Gelernter J (2011) Association of CHRNA4 polymorphisms with smoking behavior in two populations. Am J Med Genet B Neuropsychiatr Genet 156B:421-429.
6. Harkness PC and Millar NS (2002) Changes in conformation and subcellular distribution of alpha4beta2 nicotinic acetylcholine receptors revealed by chronic nicotine treatment and expression of subunit chimeras. J Neurosci 22:10172-10181.
7. Hu MC, Davies M, and Kandel DB (2006) Epidemiology and correlates of daily smoking and nicotine dependence among young adults in the United States. Am J Public Health 96:299-308.
8. Jeanclos EM, Lin L, Treuil MW, Rao J, DeCoster MA, and Anand R (2001) The chaperone protein 14-3-3eta interacts with the nicotinic acetylcholine receptor alpha 4 subunit. Evidence for a dynamic role in subunit stabilization. J Biol Chem 276:28281-28290.
9. Jia L, Flotildes K, Li M, and Cohen BN (2003) Nicotine trapping causes the persistent desensitization of alpha4beta2 nicotinic receptors expressed in oocytes. J Neurochem 84:753-766.
10. Kamens HM, Corley RP, McQueen MB, Stallings MC, Hopfer CJ, Crowley TJ, Brown SA, Hewitt JK, and Ehringer MA (2013) Nominal association with CHRNA4 variants and nicotine dependence. Genes Brain Behav 12:297-304 Epub ahead of print.
11. Kracun S, Harkness PC, Gibb AJ, and Millar NS (2008) Influence of the M3-M4 intracellular domain upon nicotinic acetylcholine receptor assembly, targeting and function. Br J Pharmacol 153:1474-1484.
12. Kukhtina V, Kottwitz D, Strauss H, Heise B, Chebotareva N, Tsetlin V, and Hucho F (2006) Intracellular domain of nicotinic acetylcholine receptor: the importance of being unfolded. J Neurochem 97 (Suppl 1):63-67.
13. Kuo YP, Xu L, Eaton JB, Zhao L, Wu J, and Lukas RJ (2005) Roles for nicotinic acetylcholine receptor subunit large cytoplasmic loop sequences in receptor expression and function. J Pharmacol Exp Ther 314:455-466.
14. Kuryatov A, Berrettini W, and Lindstrom J (2011) Acetylcholine receptor (AChR) a5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (a4b2)za5 AChR function. Mol Pharmacol 79:119-125.
15. Kuryatov A, Luo J, Cooper J, and Lindstrom J (2005) Nicotine acts as a pharmacological chaperone to up-regulate human alpha4beta2 acetylcholine receptors. Mol Pharmacol 68:1839-1851.
16. Lester HA, Xiao C, Srinivasan R, Son CD, Miwa J, Pantoja R, Banghart MR, Dougherty DA, Goate AM, and Wang JC (2009) Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery. AAPS J 11:167-177.
17. Lukas RJ, Changeux JP, Le Novère N, Albuquerque EX, Balfour DJ, Berg DK, Bertrand D, Chiappinelli VA, Clarke PB, and Collins AC, et al. (1999) International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits. Pharmacol Rev 51:397-401.
18. Marks MJ, Meinerz NM, Brown RW, and Collins AC (2010) 86Rb1 efflux mediated by alpha4beta2*-nicotinic acetylcholine receptors with high and low-sensitivity to stimulation by acetylcholine display similar agonist-induced desensitization. Biochem Pharmacol 80:1238-1251.
19. Marks MJ, Meinerz NM, Drago J, and Collins AC (2007) Gene targeting demonstrates that alpha4 nicotinic acetylcholine receptor subunits contribute to expression of diverse [3H]epibatidine binding sites and components of biphasic 86Rb1 efflux with high and low sensitivity to stimulation by acetylcholine. Neuropharmacology 53:390-405.
20. Marks MJ, Whiteaker P, Calcaterra J, Stitzel JA, Bullock AE, Grady SR, Picciotto MR, Changeux JP, and Collins AC (1999) Two pharmacologically distinct components of nicotinic receptor-mediated rubidium efflux in mouse brain require the beta2 subunit. J Pharmacol Exp Ther 289:1090-1103.
21. McGranahan TM, Patzlaff NE, Grady SR, Heinemann SF, and Booker TK (2011) a4b2 nicotinic acetylcholine receptors on dopaminergic neurons mediate nicotine reward and anxiety relief. J Neurosci 31:10891-10902.
22. Millar NS and Gotti C (2009) Diversity of vertebrate nicotinic acetylcholine receptors. Neuropharmacology 56:237-246.
23. Moroni M and Bermudez I (2006) Stoichiometry and pharmacology of two human alpha4beta2 nicotinic receptor types. J Mol Neurosci 30:95-96.
24. Nelson ME, Kuryatov A, Choi CH, Zhou Y, and Lindstrom J (2003) Alternate stoichiometries of alpha4beta2 nicotinic acetylcholine receptors. Mol Pharmacol 63: 332-341.
25. Nishimura AL, Mitne-Neto M, Silva HC, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JR, Gillingwater T, and Webb J, et al. (2004) A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 75:822-831.
26. Pacheco MA, Pastoor TE, and Wecker L (2003) Phosphorylation of the alpha4 subunit of human alpha4beta2 nicotinic receptors: role of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC). Brain Res Mol Brain Res 114:65-72.
27. Papke RL, Boulter J, Patrick J, and Heinemann S (1989) Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. Neuron 3:589-596.
28. Picciotto MR, Zoli M, Léna C, Bessis A, Lallemand Y, Le Novère N, Vincent P, Pich EM, Brûlet P, and Changeux JP (1995) Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. Nature 374:65-67.
29. Picciotto MR, Zoli M, Rimondini R, Léna C, Marubio LM, Pich EM, Fuxe K, and Changeux JP (1998) Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine. Nature 391:173-177.
30. Pollock VV, Pastoor T, Katnik C, Cuevas J, and Wecker L (2009) Cyclic AMPdependent protein kinase A and protein kinase C phosphorylate alpha4beta2 nicotinic receptor subunits at distinct stages of receptor formation and maturation. Neuroscience 158:1311-1325.
31. Pollock VV, Pastoor TE, and Wecker L (2007) Cyclic AMP-dependent protein kinase (PKA) phosphorylates Ser362 and 467 and protein kinase C phosphorylates Ser550 within the M3/M4 cytoplasmic domain of human nicotinic receptor alpha4 subunits. J Neurochem 103:456-466.
32. Pomerleau OF, Fagerström KO, Marks JL, Tate JC, and Pomerleau CS (2003) Development and validation of a self-rating scale for positive-and negativereinforcement smoking: The Michigan Nicotine Reinforcement Questionnaire. Nicotine Tob Res 5:711-718.
33. Richards CI, Srinivasan R, Xiao C, Mackey ED, Miwa JM, and Lester HA (2011) Trafficking of alpha4* nicotinic receptors revealed by superecliptic phluorin: effects of a beta4 amyotrophic lateral sclerosis-associated mutation and chronic exposure to nicotine. J Biol Chem 286:31241-31249.
34. Sabatelli M, Eusebi F, Al-Chalabi A, Conte A, Madia F, Luigetti M, Mancuso I, Limatola C, Trettel F, and Sobrero F, et al. (2009) Rare missense variants of neuronal nicotinic acetylcholine receptor altering receptor function are associated with sporadic amyotrophic lateral sclerosis. Hum Mol Genet 18:3997-4006.
35. Sabatelli M, Lattante S, Conte A, Marangi G, Luigetti M, Del Grande A, Chiò A, Corbo M, Giannini F, and Mandrioli J, et al. (2012) Replication of association of CHRNA4 rare variants with sporadic amyotrophic lateral sclerosis: the Italian multicentre study. Amyotroph Lateral Scler 13:580-584.
36. Saha I and Shamala N (2012) Investigating diproline segments in proteins: occurrences, conformation and classification. Biopolymers 97:54-64.
37. Srinivasan R, Pantoja R, Moss FJ, Mackey ED, Son CD, Miwa J, and Lester HA (2011) Nicotine up-regulates alpha4beta2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning. J Gen Physiol 137:59-79.
38. Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, Dubin JA, Estok K, Brenner E, and Baldwin RM, et al. (2006) Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than nonsmokers. J Neurosci 26:8707-8714.
39. Stitzel JA, Dobelis P, Jimenez M, and Collins AC (2001) Long sleep and short sleep mice differ in nicotine-stimulated 86Rb1 efflux and alpha4 nicotinic receptor subunit cDNA sequence. Pharmacogenetics 11:331-339.
40. Stitzel JA, Jimenez M, Marks MJ, Tritto T, and Collins AC (2000) Potential role of the alpha4 and alpha6 nicotinic receptor subunits in regulating nicotine-induced seizures. J Pharmacol Exp Ther 293:67-74.
41. Tapper AR, McKinney SL, Marks MJ, and Lester HA (2007) Nicotine responses in hypersensitive and knockout alpha 4 mice account for tolerance to both hypothermia and locomotor suppression in wild-type mice. Physiol Genomics 31:422-428.
42. Tapper AR, McKinney SL, Nashmi R, Schwarz J, Deshpande P, Labarca C, Whiteaker P, Marks MJ, Collins AC, and Lester HA (2004) Nicotine activation of alpha4* receptors: sufficient for reward, tolerance, and sensitization. Science 306:1029-1032.
43. Tsetlin V, Kuzmin D, and Kasheverov I (2011) Assembly of nicotinic and other Cysloop receptors. J Neurochem 116:734-741.
44. Wecker L, Guo X, Rycerz AM, and Edwards SC (2001) Cyclic AMP-dependent protein kinase (PKA) and protein kinase C phosphorylate sites in the amino acid sequence corresponding to the M3/M4 cytoplasmic domain of alpha4 neuronal nicotinic receptor subunits. J Neurochem 76:711-720.
45. Whiting PJ and Lindstrom JM (1988) Characterization of bovine and human neuronal nicotinic acetylcholine receptors using monoclonal antibodies. J Neurosci 8: 3395-3404.
46. Wilking JA, Hesterberg KG, Crouch EL, Homanics GE, and Stitzel JA (2010) Chrna4 A529 knock-in mice exhibit altered nicotine sensitivity. Pharmacogenet Genomics 20:121-130.
47. Williams DK, Stokes C, Horenstein NA, and Papke RL (2011) The effective opening of nicotinic acetylcholine receptors with single agonist binding sites. J Gen Physiol 137:369-384.
48. Xie P, Kranzler HR, Krauthammer M, Cosgrove KP, Oslin D, Anton RF, Farrer LA, Picciotto MR, Krystal JH, and Zhao H, et al. (2011) Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence. Biol Psychiatry 70:528-536.
49. Zhou Y, Nelson ME, Kuryatov A, Choi C, Cooper J, and Lindstrom J (2003) Human alpha4beta2 acetylcholine receptors formed from linked subunits. J Neurosci 23: 9004-9015.
50. Zwart R and Vijverberg HP (1998) Four pharmacologically distinct subtypes of alpha4beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes. Mol Pharmacol 54:1124-1131.