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7 - G protein functions identified using genetic mouse models

from PART III - GPCR SIGNALING FEATURES

Published online by Cambridge University Press:  05 June 2012

By
Stefan Offermanns
Edited by
Sandra Siehler  and
Graeme Milligan
Stefan Offermanns
Affiliation:
Max-Planck Institute for Heart and Lung Research
Sandra Siehler
Affiliation:
Novartis Institute for Biomedical Research
Graeme Milligan
Affiliation:
University of Glasgow
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Type
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Information
G Protein-Coupled Receptors
Structure, Signaling, and Physiology
 , pp. 125 - 144
Publisher: Cambridge University Press
Print publication year: 2010

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References

Wettschureck, N., Moers, A., Wallenwein, B., Parlow, A.F., Maser-Gluth, C., and Offermanns, S. (2005). Loss of Gq/11 family G proteins in the nervous system causes pituitary somatotroph hypoplasia and dwarfism in mice. Mol Cell Biol 25, 1942–1948.CrossRefGoogle ScholarPubMed
Sunahara, R.K., Dessauer, C.W., and Gilman, A.G. (1996). Complexity and diversity of mammalian adenylyl cyclases. Annu Rev Pharmacol Toxicol 36, 461–480.CrossRefGoogle ScholarPubMed
Clapham, D.E., and Neer, E.J. (1997). G protein beta gamma subunits. Annu Rev Pharmacol Toxicol 37, 167–203.CrossRefGoogle ScholarPubMed
Meng, J., and Casey, P.J. (2004). Signaling through Gz. In Handbook of cell signaling, Bradshaw, R.A., and Dennis, E.A., eds. (Amsterdam, Boston,Heidelberg), pp. 601–604.
Arshavsky, V.Y., Lamb, T.D., and Pugh, Jr., E.N. (2002). G proteins and phototransduction. Annu Rev Physiol 64, 153–187.CrossRefGoogle ScholarPubMed
Damak, S. (2004). G proteins mediating taste transduction. In Handbook of cell signaling, Bradshaw, R.A., and Dennis, E.A., eds. (Amsterdam, Boston, Heidelberg, Academic Press), pp. 657–661.
Rhee, S.G. (2001). Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem 70, 281–312.CrossRefGoogle ScholarPubMed
Kelly, P., Casey, P.J., and Meigs, T.E. (2007). Biologic functions of the G12 subfamily of heterotrimeric g proteins: growth, migration, and metastasis. Biochemistry 46, 6677–6687.CrossRefGoogle Scholar
Kurose, H. (2003). Galpha12 and Galpha13 as key regulatory mediator in signal transduction. Life Sci 74, 155–161.CrossRefGoogle ScholarPubMed
Worzfeld, T., Wettschureck, N., and Offermanns, S. (2008). G(12)/G(13)-mediated signalling in mammalian physiology and disease. Trends Pharmacol Sci 29, 582–589.CrossRefGoogle Scholar
Fukuhara, S., Chikumi, H., and Gutkind, J.S. (2001). RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?Oncogene 20, 1661–1668.CrossRefGoogle ScholarPubMed
Plagge, A., Kelsey, G., and Germain-Lee, E.L. (2008). Physiological functions of the imprinted Gnas locus and its protein variants Galpha(s) and XLalpha(s) in human and mouse. J Endocrinol 196, 193–214.CrossRefGoogle Scholar
Weinstein, L.S., Xie, T., Zhang, Q.H., and Chen, M. (2007). Studies of the regulation and function of the G(s)alpha gene Gnas using gene targeting technology. Pharmacol Ther 115, 271–291.CrossRefGoogle Scholar
Offermanns, S., Mancino, V., Revel, J.P., and Simon, M.I. (1997b). Vascular system defects and impaired cell chemokinesis as a result of Galpha13 deficiency. Science 275, 533–536.CrossRefGoogle ScholarPubMed
Ruppel, K.M., Willison, D., Kataoka, H., Wang, A., Zheng, Y.W., Cornelissen, I., Yin, L., Xu, S.M., and Coughlin, S.R. (2005). Essential role for Galpha13 in endothelial cells during embryonic development. Proc Natl Acad Sci U S A 102, 8281–8286.CrossRefGoogle ScholarPubMed
Moers, A., Nurnberg, A., Goebbels, S., Wettschureck, N., and Offermanns, S. (2008). Galpha12/Galpha13 deficiency causes localized overmigration of neurons in the developing cerebral and cerebellar cortices. Mol Cell Biol 28, 1480–1488.CrossRefGoogle ScholarPubMed
Kranenburg, O., Poland, M., Horck, F.P., Drechsel, D., Hall, A., and Moolenaar, W.H. (1999). Activation of RhoA by lysophosphatidic acid and Galpha12/13 subunits in neuronal cells: induction of neurite retraction. Mol Biol Cell 10, 1851–1857.CrossRefGoogle ScholarPubMed
Nürnberg, A., Bräuer, A.U., Wettschureck, N., and Offermanns, S. (2008). Antagonistic regulation of neurite morphology through Gq/G11 and G12/G13. J Biol Chem 283, 35526–35531.CrossRefGoogle ScholarPubMed
Offermanns, S., Zhao, L.P., Gohla, A., Sarosi, I., Simon, M.I., and Wilkie, T.M. (1998). Embryonic cardiomyocyte hypoplasia and craniofacial defects in G alpha q/G alpha 11-mutant mice. Embo J 17, 4304–4312.CrossRefGoogle Scholar
Dettlaff-Swiercz, D.A., Wettschureck, N., Moers, A., Huber, K., and Offermanns, S. (2005). Characteristic defects in neural crest cell-specific Galphaq/Galpha11- and Galpha12/Galpha13-deficient mice. Dev Biol 282, 174–182.CrossRefGoogle ScholarPubMed
Ivey, K., Tyson, B., Ukidwe, P., McFadden, D.G., Levi, G., Olson, E.N., Srivastava, D., and Wilkie, T.M. (2003). Galphaq and Galpha11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme. Dev Biol 255, 230–237.CrossRefGoogle ScholarPubMed
Yu, S., Yu, D., Lee, E., Eckhaus, M., Lee, R., Corria, Z., Accili, D., Westphal, H., and Weinstein, L.S. (1998). Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene. Proc Natl Acad Sci U S A 95, 8715–8720.CrossRefGoogle ScholarPubMed
Weinstein, L.S., and Yu, S. (1999). The role of genomic imprinting of Galpha in the pathogenesis of Albright hereditary osteodystrophy. Trends Endocrinol Metab 10, 81–85.CrossRefGoogle ScholarPubMed
Gohla, A., Klement, K., Piekorz, R.P., Pexa, K., vom Dahl, S., Spicher, K., Dreval, V., Haussinger, D., Birnbaumer, L., and Nurnberg, B. (2007). An obligatory requirement for the heterotrimeric G protein Gi3 in the antiautophagic action of insulin in the liver. Proc Natl Acad Sci U S A 104, 3003–3008.CrossRefGoogle ScholarPubMed
Jiang, M., Gold, M.S., Boulay, G., Spicher, K., Peyton, M., Brabet, P., Srinivasan, Y., Rudolph, U., Ellison, G., and Birnbaumer, L. (1998). Multiple neurological abnormalities in mice deficient in the G protein Go. Proc Natl Acad Sci U S A 95, 3269–3274.CrossRefGoogle ScholarPubMed
Valenzuela, D., Han, X., Mende, U., Fankhauser, C., Mashimo, H., Huang, P., Pfeffer, J., Neer, E.J., and Fishman, M.C. (1997). G alpha(o) is necessary for muscarinic regulation of Ca2+ channels in mouse heart. Proc Natl Acad Sci U S A 94, 1727–1732.CrossRefGoogle Scholar
Dhingra, A., Jiang, M., Wang, T.L., Lyubarsky, A., Savchenko, A., Bar-Yehuda, T., Sterling, P., Birnbaumer, L., and Vardi, N. (2002). Light response of retinal ON bipolar cells requires a specific splice variant of Galpha(o). J Neurosci 22, 4878–4884.CrossRefGoogle Scholar
Dhingra, A., Lyubarsky, A., Jiang, M., Pugh, E.N., Jr., Birnbaumer, L., Sterling, P., and Vardi, N. (2000). The light response of ON bipolar neurons requires G[alpha]o. J Neurosci 20, 9053–9058.CrossRefGoogle Scholar
Hendry, I.A., Kelleher, K.L., Bartlett, S.E., Leck, K.J., Reynolds, A.J., Heydon, K., Mellick, A., Megirian, D., and Matthaei, K.I. (2000). Hypertolerance to morphine in G(z alpha)-deficient mice. Brain Res 870, 10–19.CrossRefGoogle Scholar
Yang, J., Wu, J., Kowalska, M.A., Dalvi, A., Prevost, N., O'Brien, P.J., Manning, D., Poncz, M., Lucki, I., Blendy, J.A., et al. (2000). Loss of signaling through the G protein, Gz, results in abnormal platelet activation and altered responses to psychoactive drugs. Proc Natl Acad Sci U S A 97, 9984–9989.CrossRefGoogle Scholar
Belluscio, L., Gold, G.H., Nemes, A., and Axel, R. (1998). Mice deficient in G(olf) are anosmic. Neuron 20, 69–81.CrossRefGoogle Scholar
Corvol, J.C., Studler, J.M., Schonn, J.S., Girault, J.A., and Herve, D. (2001). Galpha(olf) is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum. J Neurochem 76, 1585–1588.CrossRefGoogle ScholarPubMed
Zhuang, X., Belluscio, L., and Hen, R. (2000). G(olf)alpha mediates dopamine D1 receptor signaling. J Neurosci 20, RC91.CrossRefGoogle Scholar
Hartmann, J., Blum, R., Kovalchuk, Y., Adelsberger, H., Kuner, R., Durand, G.M., Miyata, M., Kano, M., Offermanns, S., and Konnerth, A. (2004). Distinct roles of Galpha(q) and Galpha11 for Purkinje cell signaling and motor behavior. J Neurosci 24, 5119–5130.CrossRefGoogle ScholarPubMed
Offermanns, S., Hashimoto, K., Watanabe, M., Sun, W., Kurihara, H., Thompson, R.F., Inoue, Y., Kano, M., and Simon, M.I. (1997a). Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galphaq. Proc Natl Acad Sci U S A 94, 14089–14094.CrossRefGoogle ScholarPubMed
Boyden, E.S., Katoh, A., and Raymond, J.L. (2004). Cerebellum-dependent learning: the role of multiple plasticity mechanisms. Annu Rev Neurosci 27, 581–609.CrossRefGoogle ScholarPubMed
Miura, M., Watanabe, M., Offermanns, S., Simon, M.I., and Kano, M. (2002). Group I metabotropic glutamate receptor signaling via Galpha q/Galpha 11 secures the induction of long-term potentiation in the hippocampal area CA1. J Neurosci 22, 8379–8390.CrossRefGoogle Scholar
Kleppisch, T., Voigt, V., Allmann, R., and Offermanns, S. (2001). G(alpha)q-deficient mice lack metabotropic glutamate receptor-dependent long-term depression but show normal long-term potentiation in the hippocampal CA1 region. J Neurosci 21, 4943–4948.CrossRefGoogle Scholar
Wettschureck, N., Stelt, M., Tsubokawa, H., Krestel, H., Moers, A., Petrosino, S., Schutz, G., Di Marzo, V., and Offermanns, S. (2006). Forebrain-specific inactivation of Gq/G11 family G proteins results in age-dependent epilepsy and impaired endocannabinoid formation. Mol Cell Biol 26, 5888–5894.CrossRefGoogle ScholarPubMed
Adams, G.B., Alley, I.R., Chung, U.I., Chabner, K.T., Jeanson, N.T., Lo Celso, C., Marsters, E.S., Chen, M., Weinstein, L.S., Lin, C.P., et al. (2009). Haematopoietic stem cells depend on Galpha(s)-mediated signalling to engraft bone marrow. Nature 459, 103–107.CrossRefGoogle ScholarPubMed
North, T.E., Goessling, W., Walkley, C.R., Lengerke, C., Kopani, K.R., Lord, A.M., Weber, G.J., Bowman, T.V., Jang, I.H., Grosser, T., et al. (2007). Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 447, 1007–1011.CrossRefGoogle ScholarPubMed
Rudolph, U., Finegold, M.J., Rich, S.S., Harriman, G.R., Srinivasan, Y., Brabet, P., Bradley, A., and Birnbaumer, L. (1995). Gi2 alpha protein deficiency: a model of inflammatory bowel disease. Journal of clinical immunology 15, 101S–105S.CrossRefGoogle ScholarPubMed
Hornquist, C.E., Lu, X., Rogers-Fani, P.M., Rudolph, U., Shappell, S., Birnbaumer, L., and Harriman, G.R. (1997). G(alpha)i2-deficient mice with colitis exhibit a local increase in memory CD4+ T cells and proinflammatory Th1-type cytokines. J Immunol 158, 1068–1077.Google Scholar
Han, S.B., Moratz, C., Huang, N.N., Kelsall, B., Cho, H., Shi, C.S., Schwartz, O., and Kehrl, J.H. (2005). Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles. Immunity 22, 343–354.CrossRefGoogle Scholar
Hwang, I.Y., Park, C., and Kehrl, J.H. (2007). Impaired trafficking of Gnai2+/- and Gnai2-/- T lymphocytes: implications for T cell movement within lymph nodes. J Immunol 179, 439–448.CrossRefGoogle Scholar
Rieken, S., Sassmann, A., Herroeder, S., Wallenwein, B., Moers, A., Offermanns, S., and Wettschureck, N. (2006b). G12/G13 family G proteins regulate marginal zone B cell maturation, migration, and polarization. J Immunol 177, 2985–2993.CrossRefGoogle Scholar
Rieken, S., Herroeder, S., Sassmann, A., Wallenwein, B., Moers, A., Offermanns, S., and Wettschureck, N. (2006a). Lysophospholipids control integrin-dependent adhesion in splenic B cells through G(i) and G(12)/G(13) family G-proteins but not through G(q)/G(11). J Biol Chem 281, 36985–36992.CrossRefGoogle Scholar
Herroeder, S., Reichardt, P., Sassmann, A., Zimmermann, B., Jaeneke, D., Hoeckner, J., Hollmann, M.W., Fischer, K.D., Vogt, S., Grosse, R., et al. (2009). Guanine nucleotide-binding proteins of the G12 family shape immune functions by controlling CD4+ T cell adhesiveness and motility. Immunity 30, 708–720.CrossRefGoogle ScholarPubMed
Xu, J., Wang, F., Keymeulen, A., Herzmark, P., Straight, A., Kelly, K., Takuwa, Y., Sugimoto, N., Mitchison, T., and Bourne, H.R. (2003). Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114, 201–214.CrossRefGoogle ScholarPubMed
Frey, N., and Olson, E.N. (2003). Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 65, 45–79.CrossRefGoogle ScholarPubMed
D'Angelo, D.D., Sakata, Y., Lorenz, J.N., Boivin, G.P., Walsh, R.A., Liggett, S.B., and Dorn, G.W. (1997). Transgenic Galphaq overexpression induces cardiac contractile failure in mice. Proc Natl Acad Sci U S A 94, 8121–8126.CrossRefGoogle ScholarPubMed
Mende, U., Kagen, A., Cohen, A., Aramburu, J., Schoen, F.J., and Neer, E.J. (1998). Transient cardiac expression of constitutively active Galphaq leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways. Proc Natl Acad Sci U S A 95, 13893–13898.CrossRefGoogle ScholarPubMed
Fan, G., Jiang, Y.P., Lu, Z., Martin, D.W., Kelly, D.J., Zuckerman, J.M., Ballou, L.M., Cohen, I.S., and Lin, R.Z. (2005a). A transgenic mouse model of heart failure using inducible Galpha q. J Biol Chem 280, 40337–40346.CrossRefGoogle ScholarPubMed
Syed, F., Odley, A., Hahn, H.S., Brunskill, E.W., Lynch, R.A., Marreez, Y., Sanbe, A., Robbins, J., and Dorn, G.W. (2004). Physiological growth synergizes with pathological genes in experimental cardiomyopathy. Circ Res 95, 1200–1206.CrossRefGoogle ScholarPubMed
Akhter, S.A., Luttrell, L.M., Rockman, H.A., Iaccarino, G., Lefkowitz, R.J., and Koch, W.J. (1998). Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy. Science 280, 574–577.CrossRefGoogle ScholarPubMed
Wettschureck, N., Rutten, H., Zywietz, A., Gehring, D., Wilkie, T.M., Chen, J., Chien, K.R., and Offermanns, S. (2001). Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes. Nat Med 7, 1236–1240.CrossRefGoogle ScholarPubMed
Zuberi, Z., Birnbaumer, L., and Tinker, A. (2008). The role of inhibitory heterotrimeric G proteins in the control of in vivo heart rate dynamics. Am J Physiol Regul Integr Comp Physiol 295, R1822–1830.CrossRefGoogle ScholarPubMed
Chen, F., Spicher, K., Jiang, M., Birnbaumer, L., and Wetzel, G.T. (2001). Lack of muscarinic regulation of Ca(2+) channels in G(i2)alpha gene knockout mouse hearts. Am J Physiol Heart Circ Physiol 280, H1989–1995.CrossRefGoogle Scholar
Maguire, J.J., and Davenport, A.P. (2005). Regulation of vascular reactivity by established and emerging GPCRs. Trends Pharmacol Sci 26, 448–454.Google ScholarPubMed
Somlyo, A.P., and Somlyo, A.V. (2003). Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83, 1325–1358.CrossRefGoogle ScholarPubMed
Wirth, A., Benyo, Z., Lukasova, M., Leutgeb, B., Wettschureck, N., Gorbey, S., Orsy, P., Horvath, B., Maser-Gluth, C., Greiner, E., et al. (2008). G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat Med 14, 64–68.CrossRefGoogle ScholarPubMed
Korhonen, H., Fisslthaler, B., Moers, A., Wirth, A., Habermehl, D., Wieland, T., Schutz, G., Wettschureck, N., Fleming, I., and Offermanns, S. (2009). Anaphylactic shock depends on endothelial Gq/G11. J Exp Med 206, 411–420.CrossRefGoogle ScholarPubMed
Pero, R.S., Borchers, M.T., Spicher, K., Ochkur, S.I., Sikora, L., Rao, S.P., Abdala-Valencia, H., O'Neill, K.R., Shen, H., McGarry, M.P., et al. (2007). Galphai2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation. Proc Natl Acad Sci U S A 104, 4371–4376.CrossRefGoogle ScholarPubMed
Warnock, R.A., Askari, S., Butcher, E.C., and Andrian, U.H. (1998). Molecular mechanisms of lymphocyte homing to peripheral lymph nodes. J Exp Med 187, 205–216.CrossRefGoogle ScholarPubMed
Allgeier, A., Offermanns, S., Sande, J., Spicher, K., Schultz, G., and Dumont, J.E. (1994). The human thyrotropin receptor activates G-proteins Gs and Gq/11. J Biol Chem 269, 13733–13735.Google ScholarPubMed
Laugwitz, K.L., Allgeier, A., Offermanns, S., Spicher, K., Sande, J., Dumont, J.E., and Schultz, G. (1996). The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. Proc Natl Acad Sci U S A 93, 116–120.CrossRefGoogle ScholarPubMed
Tonacchera, M., Sande, J., Parma, J., Duprez, L., Cetani, F., Costagliola, S., Dumont, J.E., and Vassart, G. (1996). TSH receptor and disease. Clin Endocrinol (Oxf) 44, 621–633.CrossRefGoogle ScholarPubMed
Kero, J., Ahmed, K., Wettschureck, N., Tunaru, S., Wintermantel, T., Greiner, E., Schutz, G., and Offermanns, S. (2007). Thyrocyte-specific G(q)/G(11) deficiency impairs thyroid function and prevents goiter development. J Clin Invest 117, 2399–2407.CrossRefGoogle Scholar
Sassmann, A, Gier, B, Grone, HJ, Drews, G, Offermanns S and Wettschureck N (2010) The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice. J Clin Invest doi:10.1172/JCI41541 [epub ahead of print].
Weinstein, L.S. (1999). Gs alpha knockouts in mice and man. Rinsho byori 47, 425–429.Google ScholarPubMed
Weinstein, L.S., Liu, J., Sakamoto, A., Xie, T., and Chen, M. (2004). GNAS: Normal and abnormal functions. Endocrinology 145, 5459–5464.CrossRefGoogle ScholarPubMed
Xie, T., Chen, M., Zhang, Q.H., Ma, Z., and Weinstein, L.S. (2007). Beta cell-specific deficiency of the stimulatory G protein alpha-subunit Gsalpha leads to reduced beta cell mass and insulin-deficient diabetes. Proc Natl Acad Sci U S A 104, 19601–19606.CrossRefGoogle ScholarPubMed
Chen, M., Gavrilova, O., Zhao, W.-Q., Nguyen, A., Lorenzo, J., Shen, L., Nackers, L., Pack, S., Jou, W., and Weinstein, L.S. (2005). Increased glucose tolerance and reduced adiposity in the absence of fasting hypoglycemia in mice with liver-specific Gsalpha deficiency. J Clin Invest 115, 3217–3227.CrossRefGoogle Scholar
Chen, M., Wang, J., Dickerson, K.E., Kelleher, J., Xie, T., Gupta, D., Lai, E.W., Pacak, K., Gavrilova, O., and Weinstein, L.S. (2009). Central nervous system imprinting of the G protein G(s)alpha and its role in metabolic regulation. Cell Metab 9, 548–555.CrossRefGoogle Scholar
Chen, M, Chen, H, Nguyen, A, Gupta, D, Wang, J, Lai, EW, Pacak, K, Gavrilova, O, Quon, MJ and Weinstein, LS (2010) G(s)alpha deficiency in adipose tissue leads to a lean phenotype with divergent effects on cold tolerance and diet-induced thermogenesis. Cell Metab 11, 320–330.CrossRefGoogle Scholar
Tanaka, M., Treloar, H., Kalb, R.G., Greer, C.A., and Strittmatter, S.M. (1999). G(o) protein-dependent survival of primary accessory olfactory neurons. Proc Natl Acad Sci U S A 96, 14106–14111.CrossRefGoogle Scholar
Calvert, P.D., Krasnoperova, N.V., Lyubarsky, A.L., Isayama, T., Nicolo, M., Kosaras, B., Wong, G., Gannon, K.S., Margolskee, R.F., Sidman, R.L., et al. (2000). Phototransduction in transgenic mice after targeted deletion of the rod transducin alpha -subunit. Proc Natl Acad Sci U S A 97, 13913–13918.CrossRefGoogle ScholarPubMed
Wong, G.T., Gannon, K.S., and Margolskee, R.F. (1996). Transduction of bitter and sweet taste by gustducin. Nature 381, 796–800.CrossRefGoogle ScholarPubMed
Ruiz-Avila, L., Wong, G.T., Damak, S., and Margolskee, R.F. (2001). Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in alpha-gustducin. Proc Natl Acad Sci U S A 98, 8868–8873.CrossRefGoogle ScholarPubMed
Jang, H.J., Kokrashvili, Z., Theodorakis, M.J., Carlson, O.D., Kim, B.J., Zhou, J., Kim, H.H., Xu, X., Chan, S.L., Juhaszova, M., et al. (2007). Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A 104,15069–15074.CrossRefGoogle ScholarPubMed
Margolskee, R.F., Dyer, J., Kokrashvili, Z., Salmon, K.S., Ilegems, E., Daly, K., Maillet, E.L., Ninomiya, Y., Mosinger, B., and Shirazi-Beechey, S.P. (2007). T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A 104, 15075–15080.CrossRefGoogle ScholarPubMed
Offermanns, S., Toombs, C.F., Hu, Y.H., and Simon, M.I. (1997c). Defective platelet activation in G alpha(q)-deficient mice. Nature 389, 183–186.CrossRefGoogle Scholar
Klages, B., Brandt, U., Simon, M.I., Schultz, G., and Offermanns, S. (1999). Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. J Cell Biol 144, 745–754.CrossRefGoogle ScholarPubMed
Jantzen, H.M., Milstone, D.S., Gousset, L., Conley, P.B., and Mortensen, R.M. (2001). Impaired activation of murine platelets lacking G alpha(i2). J Clin Invest 108, 477–483.CrossRefGoogle Scholar
Yang, J., Wu, J., Jiang, H., Mortensen, R., Austin, S., Manning, D.R., Woulfe, D., and Brass, L.F. (2002). Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem 277, 46035–46042.CrossRefGoogle ScholarPubMed
Moers, A., Nieswandt, B., Massberg, S., Wettschureck, N., Gruner, S., Konrad, I., Schulte, V., Aktas, B., Gratacap, M.P., Simon, M.I., et al. (2003). G13 is an essential mediator of platelet activation in hemostasis and thrombosis. Nat Med 9, 1418–1422.CrossRefGoogle ScholarPubMed
Moers, A., Wettschureck, N., Gruner, S., Nieswandt, B., and Offermanns, S. (2004). Unresponsiveness of platelets lacking both G{alpha}q and G{alpha}13: implications for collagen-induced platelet activation. J Biol Chem 279, 45354–45359.CrossRefGoogle Scholar
Sakamoto, A., Chen, M., Nakamura, T., Xie, T., Karsenty, G., and Weinstein, L.S. (2005b). Deficiency of the G-protein alpha-subunit G(s)alpha in osteoblasts leads to differential effects on trabecular and cortical bone. J Biol Chem 280, 21369–21375.CrossRefGoogle Scholar
Sakamoto, A., Chen, M., Kobayashi, T., Kronenberg, H.M., and Weinstein, L.S. (2005a). Chondrocyte-specific knockout of the G protein G(s)alpha leads to epiphyseal and growth plate abnormalities and ectopic chondrocyte formation. J Bone Miner Res 20, 663–671.CrossRefGoogle Scholar
Chen, L., Kim, S.M., Oppermann, M., Faulhaber-Walter, R., Huang, Y., Mizel, D., Chen, M., Lopez, M.L., Weinstein, L.S., Gomez, R.A., et al. (2007). Regulation of renin in mice with Cre recombinase-mediated deletion of G protein Gsalpha in juxtaglomerular cells. Am J Physiol 292, F27–37.Google ScholarPubMed
Plagge, A., Gordon, E., Dean, W., Boiani, R., Cinti, S., Peters, J., and Kelsey, G. (2004). The imprinted signaling protein XL alpha s is required for postnatal adaptation to feeding. Nat Genet 36, 818–826.CrossRefGoogle Scholar
Xie, T., Plagge, A., Gavrilova, O., Pack, S., Jou, W., Lai, E.W., Frontera, M., Kelsey, G., and Weinstein, L.S. (2006). The alternative stimulatory G protein alpha-subunit XLalphas is a critical regulator of energy and glucose metabolism and sympathetic nerve activity in adult mice. J Biol Chem 281, 18989–18999.CrossRefGoogle ScholarPubMed
Pineda, V.V., Athos, J.I., Wang, H., Celver, J., Ippolito, D., Boulay, G., Birnbaumer, L., and Storm, D.R. (2004). Removal of G(ialpha1) constraints on adenylyl cyclase in the hippocampus enhances LTP and impairs memory formation. Neuron 41, 153–163.CrossRefGoogle Scholar
He, J., Gurunathan, S., Iwasaki, A., Ash-Shaheed, B., and Kelsall, B.L. (2000). Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses. J Exp Med 191, 1605–1610.CrossRefGoogle ScholarPubMed
Chang, B., Dacey, M.S., Hawes, N.L., Hitchcock, P.F., Milam, A.H., Atmaca-Sonmez, P., Nusinowitz, S., and Heckenlively, J.R. (2006). Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2. Invest Ophthalmol Vis Sci 47, 5017–5021.CrossRefGoogle ScholarPubMed
Fan, H., Zingarelli, B., Peck, O.M., Teti, G., Tempel, G.E., Halushka, P.V., Spicher, K., Boulay, G., Birnbaumer, L., and Cook, J.A. (2005b). Lipopolysaccharide- and gram-positive bacteria-induced cellular inflammatory responses: role of heterotrimeric Galpha(i) proteins. Am J Physiol Cell Physiol 289, C293–301.CrossRefGoogle ScholarPubMed
Davignon, I., Catalina, M.D., Smith, D., Montgomery, J., Swantek, J., Croy, J., Siegelman, M., and Wilkie, T.M. (2000). Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Galpha15 knockout mice. Mol Cell Biol 20, 797–804.CrossRefGoogle ScholarPubMed
Wettschureck, N., Moers, A., Hamalainen, T., Lemberger, T., Schutz, G., and Offermanns, S. (2004). Heterotrimeric G proteins of the Gq/11 family are crucial for the induction of maternal behavior in mice. Mol Cell Biol 24, 8048–8054.CrossRefGoogle ScholarPubMed
Wettschureck, N., Lee, E., Libutti, S.K., Offermanns, S., Robey, P.G., and Spiegel, A.M. (2007). Parathyroid-specific double knockout of Gq and G11 alpha-subunits leads to a phenotype resembling germline knockout of the extracellular Ca2+ -sensing receptor. Mol Endocrinol 21, 274–280.CrossRefGoogle ScholarPubMed
Gu, J.L., Muller, S., Mancino, V., Offermanns, S., and Simon, M.I. (2002). Interaction of G alpha(12) with G alpha(13) and G alpha(q) signaling pathways. Proc Natl Acad Sci U S A 99, 9352–9357.CrossRefGoogle Scholar
Wirth, A., Benyó, Z., Lukasova, M., Leutgeb, B., Wettschureck, N., Gorbey, S., Örsy, P., Horváth, B., Maser-Gluth, C., Greiner, E., et al. (2007). G12/G13-LARG-mediated signalling in vascular smooth muscle is required for salt-induced hypertension. Nat Medin press.Google Scholar
Wettschureck, N., and Offermanns, S. (2005). Mammalian G proteins and their cell type specific functions. Physiol Rev 85, 1159–1204.CrossRefGoogle ScholarPubMed

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