Toward identifying specific roles for G-protein β and γ subunit variants in olfactory reception

G-proteins mediate many cellular signaling processes; some are restricted to certain tissues or cell types, whereas others are involved in more general activities. For example, information regarding a change in the concentration of peptides, hormones, lipids, neurotransmitters, ions, odorants and tastants or an influx of photons to the eye can be transmitted to a cell via G-proteins. Heterotrimeric G proteins are composed of three subunits: Gα, Gβ and Gγ. When activated, the Gα subunit binding GTP, and the Gβγ heterodimer act on their effectors. In both vertebrates and invertebrates, many genes encode different variants of each subunit. In mammals, 20 genes encode the Gα, 5 Gβ, and 12 Gγ subunits (Malbon, 2005; Dupre et al., 2009), and there is also a considerable amount of variability in more simple organisms, such as Drosophila melanogaster, with 6 genes for Gα, 3 for Gβ and 2 for Gγ (Wolfgang et al., 1990; Yarfitz et al., 1991; Schulz et al., 1999; Boto et al., 2010). Expression studies generally offer basic information on the possible biological function of gene products and have been extensively applied to G-proteins in many species. Previous reports have confirmed that gene expression is cell specific in some cases. For example, in Drosophila, the Gαq-1 isoform (Lee et al., 1994) and the Gβ76C subunit (Yarfitz et al., 1991) were found to be specifically expressed in photoreceptor cells, highlighting their role in phototransduction. The possibility of relating specific expression of certain genes (specially for the less known Gβ and Gγ subunits) with particular functions in a comprehensive way is both a very interesting and hot issue for very different fields (see for example, O’Neill et al., 2012; El-Haibi et al., 2013). The attempt to relate particular Gβ and Gγ variants with olfactory reception tissues in mice is in the basis of the article by Sathyanesan et al. recently published in Frontiers in Cellular Neuroscience (2013, 7, 84). In many vertebrates, olfactory reception is mediated by odorant receptors that belong to the G-protein-coupled receptor (GPCR) family (Mombaerts, 1999). The expression pattern and functional roles for Gα proteins in olfactory reception have been deeply studied. Golf was found to be highly and almost exclusively expressed in olfactory receptor neurons (ORNs) of the main olfactory epithelium (MOE) (Jones and Reed, 1987), and a lack of Go in the vomeronasal organ (VNO) of mice elicits behavioral deficits (Chamero et al., 2011). However, the Gβγ subunits are not well-studied in mice, and only a few reports refer to the gene or protein expression of particular variants (Kulaga et al., 2004; Lin et al., 2007; Kerr et al., 2008; Li et al., 2013). The Gβγ heterodimer is a functional structure that, unlike Gα, does not change its conformational state when it dissociates from the heterotrimer. In vitro studies show a high variability of possible Gβ and Gγ combinations, though the possibilities are more restricted in the native situation (Milligan and Kostenis, 2006). In their paper in Frontiers in Cellular Neuroscience, Sathyanesan et al. (2013) performed a comprehensive study of the expression pattern of all Gβand Gγ-encoding genes (17) in mice olfactory receptor epithelia, MOE and VNO, in adult animals and also at different postnatal stages. To this end, the researchers analyzed gene expression by RT-PCR and quantitative PCR using RNA extracted from both organs and designing specific primers for each Gβ and Gγ subunit based on the 3′ UTR region in an attempt to overcome possible homology. The authors reported strong expression of the β1, γ8, and γ13 genes in MOE, confirming previous results from other studies (Lin et al., 2007; Kerr et al., 2008), and also detected for the first time the expression of Gβ2,4 and 5 and Gγ2,3,5,10,11, and 12 in this tissue. A quantitative analysis confirmed that β1, γ8 and γ13 are the most abundant transcripts in the main olfactory epithelium of the mouse. Sathyanesan et al. similarly analyzed the expression of the Gβ and Gγ subunits in VNO, and their results showed the expression of only Gβ1 among the Gβ group (and perhaps a very weak signal for Gβ2), and the strong presence of Gγ2,3,8, and 13. These data are based on the total RNA present in the organs. Thus, for further detail on the presence of distinct G proteins in different cell types in these olfactory organs, the authors performed in situ RNA hybridization experiments (RISH) to localize the Gβ and Gγ transcripts to specific cells. Although the RISH results did not consistently agree with the data from