title: GPCR Heterodimerization in the Reproductive System: Functional Regulation and Implication for Biodiversity.
abstract: A G protein-coupled receptor (GPCR) functions not only as a monomer or homodimer but also as a heterodimer with another GPCR. GPCR heterodimerization results in the modulation of the molecular functions of the GPCR protomer, including ligand binding affinity, signal transduction, and internalization. There has been a growing body of reports on heterodimerization of multiple GPCRs expressed in the reproductive system and the resultant functional modulation, suggesting that GPCR heterodimerization is closely associated with reproduction including the secretion of hormones and the growth and maturation of follicles and oocytes. Moreover, studies on heterodimerization among paralogs of gonadotropin-releasing hormone (GnRH) receptors of a protochordate, Ciona intestinalis, verified the species-specific regulation of the functions of GPCRs via multiple GnRH receptor pairs. These findings indicate that GPCR heterodimerization is also involved in creating biodiversity. In this review, we provide basic and current knowledge regarding GPCR heterodimers and their functional modulation, and explore the biological significance of GPCR heterodimerization.
authors: Suntory Foundation for Life Sciences, Bioorganic Research Institute , Osaka , Japan.
authors: Honoo
authors: H
authors: Satake
authors: Shin
authors: S
authors: Matsubara
authors: Masato
authors: M
authors: Aoyama
authors: Tsuyoshi
authors: T
authors: Kawada
authors: Tsubasa
authors: T
authors: Sakai
keywords: GPCR; diversity hormones; heterodimer; reproduction
references: Mol Cell Endocrinol. 2011 Jan 30;332(1-2):67-77
references: 20932877
references: Front Endocrinol (Lausanne). 2011 Feb 01;2:2
references: 22649357
references: Curr Med Chem. 2012;19(3):356-63
references: 22335512
references: Expert Opin Drug Discov. 2010 May;5(5):461-74
references: 22823130
references: J Clin Invest. 2006 May;116(5):1400-9
references: 16670773
references: PLoS One. 2012;7(7):e41955
references: 22848672
references: Adv Exp Med Biol. 2013;784:9-26
references: 23550000
references: Cell. 2001 Aug 10;106(3):381-90
references: 11509186
references: Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):654-9
references: 17194762
references: Acta Physiol (Oxf). 2008 May;193(1):3-15
references: 18284378
references: FEBS J. 2005 Jun;272(12):2947-55
references: 15955055
references: Peptides. 2012 Mar;34(1):186-92
references: 21827805
references: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5098-103
references: 21385944
references: Hum Reprod. 2007 Jun;22(6):1617-25
references: 17437961
references: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14258-63
references: 15353592
references: J Biol Chem. 2003 Dec 19;278(51):51630-7
references: 14532289
references: Pharmacol Rev. 2007 Mar;59(1):5-13
references: 17329545
references: Endocrinology. 2005 Sep;146(9):4061-73
references: 15961566
references: J Neurosci. 2000 Nov 15;20(22):RC110
references: 11069979
references: Front Endocrinol (Lausanne). 2013 Mar 08;4:24
references: 23482509
references: Endocrinology. 2012 Oct;153(10):4978-89
references: 22903610
references: Mol Biol Evol. 2010 May;27(5):1097-106
references: 20026483
references: Curr Med Chem. 2004 Aug;11(15):2045-81
references: 15279567
references: Endocrinology. 2012 Nov;153(11):5428-39
references: 23011920
references: Endocrinology. 2012 Oct;153(10):4883-93
references: 22893725
references: Neuroendocrinology. 2012;95(4):277-88
references: 22327910
references: Front Endocrinol (Lausanne). 2011 Jul 12;2:16
references: 22649364
references: Nature. 2000 Sep 7;407(6800):94-8
references: 10993080
references: EMBO J. 2006 Jul 12;25(13):3012-23
references: 16778767
references: Eur J Pharmacol. 2008 Dec 28;601(1-3):148-53
references: 18977217
references: Pharmacol Rev. 2002 Jun;54(2):285-322
references: 12037144
references: Vascul Pharmacol. 2006 Oct;45(4):200-8
references: 16931167
references: Front Neuroendocrinol. 2008 Jan;29(1):17-35
references: 17976709
references: J Biol Chem. 2006 Dec 15;281(50):38812-24
references: 17015451
references: Trends Pharmacol Sci. 2007 Dec;28(12):615-20
references: 18022255
references: Nat Genet. 2009 Mar;41(3):354-358
references: 19079066
references: Mini Rev Med Chem. 2012 Aug;12(9):817-30
references: 22681252
references: Endocrinology. 2012 Oct;153(10):4894-904
references: 22903614
references: Nature. 1998 Dec 17;396(6712):683-7
references: 9872317
references: Front Endocrinol (Lausanne). 2012 Nov 19;3:140
references: 23181055
references: J Biol Chem. 2005 Nov 18;280(46):38478-88
references: 16159882
references: Methods Enzymol. 2013;521:281-94
references: 23351745
references: Front Endocrinol (Lausanne). 2012 Nov 28;3:148
references: 23233850
references: Gen Comp Endocrinol. 2012 Jul 1;177(3):305-14
references: 22391238
references: Nat Med. 2010 Dec;16(12):1393-5
references: 21113156
references: Front Pharmacol. 2010 Sep 09;1:114
references: 21607065
references: Curr Drug Targets. 2006 Aug;7(8):963-74
references: 16918325
references: Brain Res. 2010 Dec 10;1364:116-28
references: 20800582
references: Endocrinology. 2003 May;144(5):1907-19
references: 12697698
references: Reprod Biol Endocrinol. 2010 Aug 26;8:104
references: 20796280
references: Protein Pept Lett. 2008;15(3):300-8
references: 18336362
references: Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):9050-5
references: 15932946
references: J Biol Chem. 2011 Nov 11;286(45):39623-31
references: 21940628
references: Br J Pharmacol. 2009 Sep;158(1):5-14
references: 19309353
references: Endocrinology. 2011 Sep;152(9):3461-70
references: 21771888
references: EMBO Rep. 2006 Nov;7(11):1094-8
references: 17077864
references: Gene. 2003 Dec 11;322:77-84
references: 14644499
references: Vet J. 2009 Sep;181(3):232-40
references: 18693121
references: Trends Pharmacol Sci. 1999 Jan;20(1):19-26
references: 10101958
references: Endocrinology. 2012 Oct;153(10):4818-29
references: 22822161
references: J Biol Chem. 2002 Feb 1;277(5):3236-41
references: 11711539
references: Peptides. 2011 Sep;32(9):1972-8
references: 21801774
references: J Biol Chem. 2004 Dec 17;279(51):53798-805
references: 15485888
references: Gen Comp Endocrinol. 2007 Aug-Sep;153(1-3):346-64
references: 17350014
references: Nature. 2002 Mar 14;416(6877):199-202
references: 11894099
references: Neuroendocrinology. 2012;95(3):223-31
references: 22156565
references: Endocrinology. 2011 Jun;152(6):2416-27
references: 21467196
references: Chem Rev. 2011 Dec 14;111(12):PR438-535
references: 22165845
references: Endocrinology. 2008 Sep;149(9):4346-56
references: 18483149
references: Nat Med. 2001 Sep;7(9):1003-9
references: 11533702
references: Physiol Rev. 1999 Oct;79(4):1193-226
references: 10508233
references: Endocrinology. 2012 Apr;153(4):1841-9
references: 22294747
references: Front Endocrinol (Lausanne). 2013 Mar 28;4:22
references: 23543285
references: Peptides. 2009 Dec;30(12):2200-5
references: 19712719
references: Neuron. 2011 Jan 13;69(1):120-31
references: 21220103
references: Biol Reprod. 2006 Sep;75(3):334-41
references: 16707771
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2319-24
references: 20080658
references: Zoolog Sci. 2013 Apr;30(4):239-47
references: 23537233
references: Protein Pept Lett. 2013 Jun;20(6):615-27
references: 22630127
references: Horm Metab Res. 2012 Jul;44(8):587-91
references: 22438212