title: Heterotrimeric G protein subunit Gγ13 is critical to olfaction.
abstract: The activation of G-protein-coupled olfactory receptors on the olfactory sensory neurons (OSNs) triggers a signaling cascade, which is mediated by a heterotrimeric G-protein consisting of α, β, and γ subunits. Although its α subunit, Gαolf, has been identified and well characterized, the identities of its β and γ subunits and their function in olfactory signal transduction, however, have not been well established yet. We, and others, have found the expression of Gγ13 in the olfactory epithelium, particularly in the cilia of the OSNs. In this study, we generated a conditional gene knock-out mouse line to specifically nullify Gγ13 expression in the olfactory marker protein-expressing OSNs. Immunohistochemical and Western blot results showed that Gγ13 subunit was indeed eliminated in the mutant mice's olfactory epithelium. Intriguingly, Gαolf, β1 subunits, Ric-8B and CEP290 proteins, were also absent in the epithelium whereas the presence of the effector enzyme adenylyl cyclase III remained largely unaltered. Electro-olfactogram studies showed that the mutant animals had greatly reduced responses to a battery of odorants including three presumable pheromones. Behavioral tests indicated that the mutant mice had a remarkably reduced ability to perform an odor-guided search task although their motivation and agility seemed normal. Our results indicate that Gαolf exclusively forms a functional heterotrimeric G-protein with Gβ1 and Gγ13 in OSNs, mediating olfactory signal transduction. The identification of the olfactory G-protein's βγ moiety has provided a novel approach to understanding the feedback regulation of olfactory signal transduction pathways as well as the control of subcellular structures of OSNs.
authors: Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA.
authors: Feng
authors: F
authors: Li
authors: Samsudeen
authors: S
authors: Ponissery-Saidu
authors: Karen K
authors: KK
authors: Yee
authors: Hong
authors: H
authors: Wang
authors: Meng-Ling
authors: ML
authors: Chen
authors: Naoko
authors: N
authors: Iguchi
authors: Genhua
authors: G
authors: Zhang
authors: Ping
authors: P
authors: Jiang
authors: Johannes
authors: J
authors: Reisert
authors: Liquan
authors: L
authors: Huang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004585:Electrooculography / Q000379:methods; D004622:Embryo, Mammalian; D005071:Evoked Potentials / Q000235:genetics; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009812:Odorants; D051842:Olfactory Marker Protein / Q000378:metabolism; D009831:Olfactory Mucosa / Q000378:metabolism; D009833:Olfactory Pathways / Q000166:cytology; D018034:Olfactory Receptor Neurons / Q000502:physiology; D011930:Reaction Time / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012903:Smell / Q000235:genetics / Q000502:physiology*
chemical_list: C118981:G-protein Beta gamma; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; C510865:Ggamma13 protein, mouse; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; C084618:olfactory G protein subunit alpha olf; D020962:Heterotrimeric GTP-Binding Proteins
references: Nat Neurosci. 2011 Nov 06;15(1):131-7
references: 22057188
references: Nat Neurosci. 2011 Jun;14(6):763-9
references: 21516098
references: Biochemistry. 2007 Jul 3;46(26):7665-77
references: 17559193
references: Front Cell Neurosci. 2012 Jun 21;6:26
references: 22737109
references: Genome Res. 2001 May;11(5):685-702
references: 11337468
references: Neuron. 1994 Sep;13(3):611-21
references: 7522482
references: Nature. 1993 Nov 18;366(6452):283-6
references: 8232590
references: Neuron. 1993 Jul;11(1):123-32
references: 8393322
references: Brain Res. 2002 Jun 21;941(1-2):62-71
references: 12031548
references: Results Probl Cell Differ. 2009;47:77-96
references: 19083125
references: J Neurosci. 2008 Mar 26;28(13):3510-20
references: 18367617
references: Neuron. 1998 Jan;20(1):69-81
references: 9459443
references: J Biol Chem. 2006 Apr 21;281(16):11066-73
references: 16473877
references: J Cell Biol. 2010 Nov 1;191(3):443-52
references: 21041441
references: Annu Rev Pharmacol Toxicol. 2009;49:31-56
references: 18834311
references: Nat Neurosci. 1999 Dec;2(12):1055-62
references: 10570481
references: Mol Cell Neurosci. 2008 Jul;38(3):341-8
references: 18462949
references: Cell. 1991 Apr 5;65(1):175-87
references: 1840504
references: Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8890-4
references: 7522325
references: Eur J Neurosci. 1996 Nov;8(11):2388-98
references: 8950102
references: J Physiol. 2007 Dec 15;585(Pt 3):731-40
references: 17932148
references: J Vis Exp. 2010 Mar 02;(37):
references: 20197755
references: Science. 1989 May 19;244(4906):790-5
references: 2499043
references: J Neurosci. 2007 Oct 3;27(40):10703-13
references: 17913904
references: J Neurosci. 2011 Feb 23;31(8):2974-82
references: 21414919
references: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9858-63
references: 8790421
references: J Physiol. 1974 Oct;242(2):353-70
references: 4549073
references: Nat Rev Neurosci. 2004 Apr;5(4):263-78
references: 15034552
references: PLoS One. 2009;4(1):e4260
references: 19165324
references: Nature. 1990 Sep 13;347(6289):184-7
references: 1697649
references: Genome Res. 2003 Mar;13(3):476-84
references: 12618378
references: Dev Biol. 2002 Mar 15;243(2):281-93
references: 11884037
references: Neuron. 1996 Oct;17(4):681-93
references: 8893025
references: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11776-81
references: 19561302
references: Science. 1990 Dec 7;250(4986):1403-6
references: 2255909
references: J Neurosci. 1999 Jul 1;19(13):5332-47
references: 10377344
references: Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12898-903
references: 21768373
references: Nat Genet. 2004 Sep;36(9):994-8
references: 15322545
references: Nature. 2004 Mar 25;428(6981):393-9
references: 15042081
references: Neuron. 2000 Sep;27(3):487-97
references: 11055432
references: J Biol Chem. 2005 Dec 16;280(50):41769-76
references: 16221676
references: Behav Neurosci. 2001 Jun;115(3):626-31
references: 11439451
references: Hum Mol Genet. 2002 Mar 1;11(5):535-46
references: 11875048
references: Nat Neurosci. 2002 Feb;5(2):124-33
references: 11802173
references: J Biol Chem. 2003 Feb 21;278(8):6575-9
references: 12488442
references: Annu Rev Physiol. 2009;71:115-40
references: 18808328
references: J Neurosci. 2011 Jun 1;31(22):8067-77
references: 21632928
references: Science. 2001 Dec 7;294(5549):2172-5
references: 11739959
references: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15917-22
references: 17898177
references: J Biol Chem. 2006 Nov 17;281(46):35156-66
references: 16980309
references: Acta Physiol Scand Suppl. 1955;35(122):1-83
references: 13301864
references: J Biol Chem. 2001 Dec 28;276(52):49267-74
references: 11675383
references: J Biol Chem. 1991 Mar 25;266(9):5363-6
references: 1706334
references: Curr Protoc Neurosci. 2009 Jul;Chapter 8:Unit 8.24
references: 19575474
references: Neuroreport. 1999 Jan 18;10(1):15-9
references: 10094125