Human GPR42 is a transcribed multisite variant that exhibits copy number polymorphism and is functional when heterologously expressed

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Puhl Iii, Henry L ^a   Won, Yu Jin ^a   Lu, Van B ^a   Ikeda, Stephen R ^a  

^a NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FFAR1 PROTEIN, HUMAN; FFAR3 PROTEIN, HUMAN; G PROTEIN COUPLED RECEPTOR;

AGONISTS; ANIMAL; BIOSYNTHESIS; COPY NUMBER VARIATION; DRUG EFFECTS; GENETICS; GENOTYPE; HAPLOTYPE; HUMAN; METABOLISM; NERVE CELL; PSEUDOGENE; RAT; SYMPATHETIC GANGLION;

ANIMALS; DNA COPY NUMBER VARIATIONS; GANGLIA, SYMPATHETIC; GENOTYPE; HAPLOTYPES; HUMANS; NEURONS; PSEUDOGENES; RATS; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84939170670     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep12880     Document Type: Article

References (51)

1. Offermanns, S. Free Fatty Acid (FFA) and Hydroxy Carboxylic Acid (HCA) Receptors. Annu Rev Pharmacol Toxicol 54, 407-434 (2014).
2. Brown, A. J., et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278, 11312-11319 (2003).
3. Le Poul, E., et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 278, 25481-25489 (2003).
4. Kimura, I., et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun 4, 1829 (2013).
5. Samuel, B. S., et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G proteincoupled receptor, Gpr41. Proc Natl Acad Sci USA 105, 16767-16772 (2008).
6. Tolhurst, G., et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364-371 (2012).
7. De Vadder, F., et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156, 84-96 (2014).
8. Trompette, A., et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 20, 159-166 (2014).
9. Tang, C., et al. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med 21, 173-177 (2015).
10. Thorburn, A. N., Macia, L. & Mackay, C. R. Diet, metabolites, and western-lifestyle inflammatory diseases. Immunity 40, 833-842 (2014).
11. Kimura, I., et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci USA 108, 8030-8035 (2011).
12. Won, Y.-J., Lu, V. B., Puhl, H. L. & Ikeda, S. R. hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3. J. Neurosci. 33, 19314-19325 (2013).
13. Nhr, M. K., et al. Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia. Neuroscience 290C, 126-137 (2015).
14. Tsukamoto, S., et al. Determinations of ethanol, acetaldehyde and acetate in blood and urine during alcohol oxidation in man. Alcohol Alcohol. 24, 101-108 (1989).
15. Siler, S. Q., Neese, R. A. & Hellerstein, M. K. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am. J. Clin. Nutr. 70, 928-936 (1999).
16. Hudson, B. D., Murdoch, H. & Milligan, G. Minireview: The effects of species ortholog and SNP variation on receptors for free fatty acids. Mol. Endocrinol. 27, 1177-1187 (2013).
17. Sawzdargo, M., et al. A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1. Biochem Biophys Res Commun 239, 543-547 (1997).
18. Liaw, C. W. & Connolly, D. T. Sequence polymorphisms provide a common consensus sequence for GPR41 and GPR42. DNA Cell Biol 28, 555-560 (2009).
19. Hudson, B. D., Tikhonova, I. G., Pandey, S. K., Ulven, T. & Milligan, G. Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3. J Biol Chem 287, 41195-41209 (2012).
20. Durbin, R. M., et al. A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073 (2010).
21. Mangan, M. E., Williams, J. M., Kuhn, R. M. & Lathe, W. C. The UCSC genome browser: what every molecular biologist should know. Curr Protoc Mol Biol Chapter 19, Unit19.9 (2009).
22. Tazoe, H., et al. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed. Res. 30, 149-156 (2009).
23. Bailey, J. A., Yavor, A. M., Massa, H. F., Trask, B. J. & Eichler, E. E. Segmental duplications: organization and impact within the current human genome project assembly. Genome Res. 11, 1005-1017 (2001).
24. Ikeda, S. R. & Dunlap, K. Voltage-dependent modulation of N-type calcium channels: role of G protein subunits. Adv Second Messenger Phosphoprotein Res 33, 131-151 (1999).
25. Pluznick, J. L., et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci USA 110, 4410-4415 (2013).
26. Ikeda, S. R. Double-pulse calcium channel current facilitation in adult rat sympathetic neurones. J Physiol (Lond) 439, 181-214 (1991).
27. Ikeda, S. R., Lovinger, D. M., McCool, B. A. & Lewis, D. L. Heterologous expression of metabotropic glutamate receptors in adult rat sympathetic neurons: subtype-specific coupling to ion channels. Neuron 14, 1029-1038 (1995).
28. Guo, J. & Ikeda, S. R. Coupling of metabotropic glutamate receptor 8 to N-type Ca2+ channels in rat sympathetic neurons. Mol. Pharmacol. 67, 1840-1851 (2005).
29. Ikeda, S. R. Voltage-dependent modulation of N-type calcium channels by G-protein βsubunits. Nature 380, 255-258 (1996).
30. Elmslie, K. S. Neurotransmitter modulation of neuronal calcium channels. J Bioenerg Biomembr 35, 477-489 (2003).
31. Zamponi, G. W. & Currie, K. P. M. Regulation of CaV2 calcium channels by G protein coupled receptors. Biochim Biophys Acta 1828, 1629-1643 (2013).
32. Hudson, B. D., Smith, N. J. & Milligan, G. Experimental challenges to targeting poorly characterized GPCRs: uncovering the therapeutic potential for free fatty acid receptors. Adv. Pharmacol. 62, 175-218 (2011).
33. Hudson, B. D., et al. Complex pharmacology of novel allosteric free fatty acid 3 receptor ligands. Mol. Pharmacol. 86, 200-210 (2014).
34. Ichimura, A., Hasegawa, S., Kasubuchi, M. & Kimura, I. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front Pharmacol 5, 236 (2014).
35. - 1000 Genomes Project Consortium et al. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56-65 (2012).
36. International HapMap Consortium et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851-861 (2007).
37. Niu, Y., et al. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell 156, 836-843 (2014).
38. Zhang, X., Goodsell, J. & Norgren, R. B. Limitations of the rhesus macaque draft genome assembly and annotation. BMC Genomics 13, 206 (2012).
39. Bailey, J. A. & Eichler, E. E. Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet 7, 552-564 (2006).
40. Freeman, J. L., et al. Copy number variation: new insights in genome diversity. Genome Res. 16, 949-961 (2006).
41. Zhang, F., Gu, W., Hurles, M. E. & Lupski, J. R. Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet 10, 451-481 (2009).
42. Handsaker, R. E., Genovese, G. & McCarroll, S. A. Large multiallelic copy number variations in humans. Nat Genet 47, 296-303 (2015).
43. Eichler, E. E. & Dunnen den, J. T. Complex SNP-related sequence variation in segmental genome duplications. Nat Genet 36, 861-866 (2004).
44. Green, R. E., et al. A draft sequence of the Neandertal genome. Science 328, 710-722 (2010).
45. Reich, D., et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053-1060 (2010).
46. Nourry, C., Grant, S. G. N. & Borg, J.-P. PDZ domain proteins: plug and play! Sci STKE 2003, RE7 (2003).
47. Cummings, J. H., Pomare, E. W., Branch, W. J., Naylor, C. P. & Macfarlane, G. T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221-1227 (1987).
48. Ikeda, S. R. & Jeong, S.-W. Use of RGS-insensitive Gα subunits to study endogenous RGS protein action on G-protein modulation of N-type calcium channels in sympathetic neurons. Meth Enzymol 389, 170-189 (2004).
49. Lu, V. B., Williams, D. J., Won, Y.-J. & Ikeda, S. R. Intranuclear microinjection of DNA into dissociated adult mammalian neurons. JoVE e1614-e1614 (2009) doi: 10.3791/1614.
50. Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391, 85-100 (1981).
51. Elmslie, K. S., Zhou, W. & Jones, S. W. LHRH and GTP- -S modify calcium current activation in bullfrog sympathetic neurons. Neuron 5, 75-80 (1990).