Title: | Heterotrimeric G protein subunit Ggamma13 is critical to olfaction |
Author(s): | Li F; Ponissery-Saidu S; Yee KK; Wang H; Chen ML; Iguchi N; Zhang G; Jiang P; Reisert J; Huang L; |
Address: | "Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA" |
DOI: | 10.1523/JNEUROSCI.5563-12.2013 |
ISSN/ISBN: | 1529-2401 (Electronic) 0270-6474 (Print) 0270-6474 (Linking) |
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 alpha, beta, and gamma subunits. Although its alpha subunit, Galphaolf, has been identified and well characterized, the identities of its beta and gamma subunits and their function in olfactory signal transduction, however, have not been well established yet. We, and others, have found the expression of Ggamma13 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 Ggamma13 expression in the olfactory marker protein-expressing OSNs. Immunohistochemical and Western blot results showed that Ggamma13 subunit was indeed eliminated in the mutant mice's olfactory epithelium. Intriguingly, Galphaolf, beta1 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 Galphaolf exclusively forms a functional heterotrimeric G-protein with Gbeta1 and Ggamma13 in OSNs, mediating olfactory signal transduction. The identification of the olfactory G-protein's betagamma 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" |
Keywords: | "Animals Animals, Newborn Electrooculography/methods Embryo, Mammalian Evoked Potentials/genetics Feeding Behavior/physiology Female GTP-Binding Protein alpha Subunits GTP-Binding Protein beta Subunits/genetics GTP-Binding Protein gamma Subunits/genetics G;" |
Notes: | "MedlineLi, Feng Ponissery-Saidu, Samsudeen Yee, Karen K Wang, Hong Chen, Meng-Ling Iguchi, Naoko Zhang, Genhua Jiang, Ping Reisert, Johannes Huang, Liquan eng R01 DC007487/DC/NIDCD NIH HHS/ DC010012/DC/NIDCD NIH HHS/ R01DC007487/DC/NIDCD NIH HHS/ R01 DC010012/DC/NIDCD NIH HHS/ P30 DC011735/DC/NIDCD NIH HHS/ R01 DC009613/DC/NIDCD NIH HHS/ R01DC009613/DC/NIDCD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2013/05/03 J Neurosci. 2013 May 1; 33(18):7975-84. doi: 10.1523/JNEUROSCI.5563-12.2013" |