Heterotrimeric G Protein Subunit Gγ13 Is Critical to Olfaction

Feng, Linyin; Ponissery-Saidu, Samsudeen; Yee, Karen K.; Wang, Hong; Chen, Meng‐Ling; Iguchi, Naoko; Zhang, Genhua; Jiang, Ping; Reisert, Johannes; Huang, Liquan

doi:10.1523/jneurosci.5563-12.2013

Cited by 71 publications

(66 citation statements)

References 57 publications

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“…We therefore asked whether odor-induced cAMP signaling is required for establishing the cilia pattern. We first examined olfactory epithelia from Gγ13 −/− mice, in which Cre-mediated ablation of Gγ13 prevents proper formation and ciliary targeting of G olf in OSNs and eliminates odor-induced electroolfactogram (EOG) signals [32]. Surprisingly, the cilia pattern remains completely intact in these animals (Figure 4A–C and Table S2), suggesting that G olf -mediated activity is not required for the formation and maintenance of the cilia pattern.…”

Section: Resultsmentioning

confidence: 99%

An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors

et al. 2015

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Summary In many sensory organs, specialized receptors are strategically arranged to enhance detection sensitivity and acuity. It is unclear whether the olfactory system utilizes a similar organizational scheme to facilitate odor detection. Curiously, olfactory sensory neurons (OSNs) in the mouse nose are differentially stimulated depending on the cell location. We therefore asked whether OSNs in different locations evolve unique structural and/or functional features to optimize odor detection and discrimination. Using immunohistochemistry, computational fluid dynamics modeling, and patch clamp recording, we discovered that OSNs situated in highly stimulated regions have much longer cilia and are more sensitive to odorants than those in weakly stimulated regions. Surprisingly, reduction in neuronal excitability or ablation of the olfactory G protein in OSNs does not alter the cilia length pattern, indicating that neither spontaneous nor odor-evoked activity is required for its establishment. Furthermore, the pattern is evident at birth, maintained into adulthood, and restored following pharmacologically induced degeneration of the olfactory epithelium, suggesting that it is intrinsically programmed. Intriguingly, type III adenylyl cyclase (ACIII), a key protein in olfactory signal transduction and ubiquitous marker for primary cilia, exhibits location-dependent gene expression levels, and genetic ablation of ACIII dramatically alters the cilia pattern. These findings reveal an intrinsically programmed configuration in the nose to ensure high sensitivity to odors.

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Section: Resultsmentioning

confidence: 99%

An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors

et al. 2015

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“…Curiously, conditional knockout of Gγ 13 in mouse olfactory sensory neurons results in dramatic down-regulation of Gα olf , Gβ 1 and the guanine nucleotide exchange factor RIC8B, as well as mislocalization of type III adenylyl cyclase to the sensory neuron soma (Li et al, 2013). In contrast, Gα olf and Gβ 1 expression is unaffected by inhibition of Gβγ signaling in zebrafish olfactory sensory neurons (this study).…”

Section: Discussionmentioning

confidence: 99%

Silencing of Odorant Receptor Genes by G Protein βγ Signaling Ensures the Expression of One Odorant Receptor per Olfactory Sensory Neuron

Ferreira

Wilson

Choi

et al. 2014

Neuron

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Summary Olfactory sensory neurons express just one out of a possible ~1000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein βγ subunits is both necessary and sufficient to suppress the expression of odorant receptor genes, and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results provide new insights linking receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron.

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“…Previously, Ryba and Tirindelli (1995) reported the expression of Gγ 8 gene transcript in cell bodies of immature OSNs (iOSNs) using RNA in situ hybridization (RISH). In addition, Gγ 13 protein is known to express strongly in cilia and cell bodies of mOSNs in the MOE, including a subset of OSNs that express TRPM5, and plays an important role in olfaction (Kulaga et al, 2004; Lin et al, 2007; Li et al, 2013). More recently, Kerr et al (2008) reported that Gβ 1 was the dominant Gβ subunit in the MOE.…”

Section: Introductionmentioning

confidence: 99%

Expression profile of G-protein βγ subunit gene transcripts in the mouse olfactory sensory epithelia

Sathyanesan¹,

Feijoo²,

Mehta³

et al. 2013

Front. Cell. Neurosci.

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Heterotrimeric G-proteins mediate a variety of cellular functions, including signal transduction in sensory neurons of the olfactory system. Whereas the Gα subunits in these neurons are well characterized, the gene transcript expression profile of Gβγ subunits is largely missing. Here we report our comprehensive expression analysis to identify Gβ and Gγ subunit gene transcripts in the mouse main olfactory epithelium (MOE) and the vomeronasal organ (VNO). Our reverse transcriptase PCR (RT-PCR) and realtime qPCR analyses of all known Gβ (β1,2,3,4,5) and Gγ (γ1,2,2t,3,4,5,7,8,10,11,12,13) subunits indicate presence of multiple Gβ and Gγ subunit gene transcripts in the MOE and the VNO at various expression levels. These results are supported by our RNA in situ hybridization (RISH) experiments, which reveal the expression patterns of two Gβ subunits and four Gγ subunits in the MOE as well as one Gβ and four Gγ subunits in the VNO. Using double-probe fluorescence RISH and line intensity scan analysis of the RISH signals of two dominant Gβγ subunits, we show that Gγ13 is expressed in mature olfactory sensory neurons (OSNs), while Gβ1 is present in both mature and immature OSNs. Interestingly, we also found Gβ1 to be the dominant Gβ subunit in the VNO and present throughout the sensory epithelium. In contrast, we found diverse expression of Gγ subunit gene transcripts with Gγ2, Gγ3, and Gγ13 in the Gαi2-expressing neuronal population, while Gγ8 is expressed in both layers. Further, we determined the expression of these Gβγ gene transcripts in three post-natal developmental stages (p0, 7, and 14) and found their cell-type specific expression remains largely unchanged, except the transient expression of Gγ2 in a single basal layer of cells in the MOE during P7 and P14. Taken together, our comprehensive expression analyses reveal cell-type specific gene expression of multiple Gβ and Gγ in sensory neurons of the olfactory system.

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Heterotrimeric G Protein Subunit Gγ13 Is Critical to Olfaction

Cited by 71 publications

References 57 publications

An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors

An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors

Silencing of Odorant Receptor Genes by G Protein βγ Signaling Ensures the Expression of One Odorant Receptor per Olfactory Sensory Neuron

Expression profile of G-protein βγ subunit gene transcripts in the mouse olfactory sensory epithelia

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