NCBI Summary:
This locus encodes a guanine nucleotide-binding protein. The encoded protein, an alpha subunit in the Gq class, couples a seven-transmembrane domain receptor to activation of phospolipase C-beta. Mutations at this locus have been associated with problems in platelet activation and aggregation. A related pseudogene exists on chromosome 2.[provided by RefSeq, Nov 2010]
General function
Intracellular signaling cascade
Comment
Cellular localization
Plasma membrane
Comment
candidate123
Ovarian function
Comment
Expression regulated by
LH
Comment
Ovarian superstimulation using FSH combined with equine chorionic gonadotropin (eCG) upregulates mRNA-encoding proteins involved with LH receptor intracellular signaling in granulosa cells from Nelore cows. Castilho AC 2014 et al.
The LH plays a key role in controlling physiological processes in the ovary acting via LH receptor (LHR). In general, the effects of LHR on the regulation of granulosa cell differentiation are mediated mainly via the Gs-protein/adenylyl cyclase/cAMP system; however, the LHR activation could also induce phospholipase C (PLC)/inositol trisphosphate (IP3) via Gq/11 system. Additionally, the expression of G-proteins (GNAS, GNAQ, and GNA11) and PLC has been showed in bovine antral follicle, concomitant with an increase in LHR expression. To gain insight into the effects of superstimulation with FSH (P-36 protocol) or FSH combined with equine chorionic gonadotropin (eCG; P-36/eCG protocol) on the mRNA expression of proteins involved in LHR signaling in bovine granulosa cells, Nelore cows (Bos indicus) were treated with two superstimulatory protocols: P-36 protocol or P-36/eCG protocol (replacement of the FSH by eCG administration on the last day of treatment). Nonsuperstimulated cows were only submitted to estrous synchronization without ovarian superstimulation. The granulosa cells were harvested from follicles and mRNA abundance of GNAS, GNAQ, GNA11, PLCB1, PLCB, PLCB4, and adenylyl cyclase isoforms (ADCY3, ADCY4, ADCY6, ADCY8, and ADCY9) was measured by real-time reserve transcription followed by polymerase chain reaction. No differences on mRNA abundance of target genes were observed in granulosa cells of cows submitted to P-36 protocol compared with control group. However, the cows submitted to P-36/eCG protocol showed upregulation on the mRNA abundance of target genes (except ADCY8) in granulosa cells. Although the P-36 protocol did not regulate mRNA expression of the proteins involved in the signaling mechanisms of the cAMP and IP3 systems, the constant presence of GNAS, GNAQ, GNA11, PLCB1, PLCB3, PLCB4, and adenylyl cyclase isoforms (ADCY3, ADCY4, ADCY6, and ADCY9) mRNA and the upregulation of these genes in granulosa cells from cows submitted to P-36/eCG protocol reinforce the participation of Gq/11/PLC/IP3 signaling as well as Gs-protein/adenylyl cyclase/cAMP system on LHR pathways during bovine granulosa cell differentiation submitted to superstimulatory treatments.
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Ovarian localization
Granulosa
Comment
Follicle stages
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: subfertile Comment: A functional GNAQ promoter haplotype is associated with altered Gq expression and with insulin resistance and obesity in women with polycystic ovary syndrome. Klenke S et al. OBJECTIVES: The G-protein Gq, encoded by GNAQ, is involved in glucose metabolism. The GNAQ promoter harbours three polymorphisms. The TT(-695/-694)GC polymorphism was already shown to affect Gq transcription. Accordingly, we (i) characterized the GNAQ promoter polymorphisms G(-173)A and G(-168)A, (ii) investigated potential influences upon the TT(-695/-694)GC polymorphism and (iii) studied the associations with metabolic abnormalities in polycystic ovary syndrome (PCOS). METHODS: Characterization of the polymorphisms was performed with electrophoretic mobility shift assays and reporter assays. Inhibition of lipolysis and Gq expression were measured in adipocytes isolated from female mammary tissue. We genotyped 266 healthy Caucasians, 265 women with PCOS, and 293 healthy, age-matched female controls to associate GNAQ promoter polymorphisms and haplotypes with anthropometric and metabolic variables. RESULTS: The A(-168) allele was associated with significantly decreased transcriptional activity and altered transcription factor binding, whereas the G(-173)A polymorphism appeared functionally silent. Linkage and haplotype frequencies analysis resulted in four common haplotypes. In adipose tissue, a 44% higher Gq mRNA concentration was observed in homozygous GC(-695/-694)-G(-168) haplotypes compared with homozygous TT(-695/-694)-G(-168) haplotypes (P=0.046). This was associated with increased insulin inhibition of lipolysis in isolated adipocytes. In PCOS patients, the homozygous GC-G haplotype was associated with decreased insulin resistance and body mass index (BMI) compared with the homozygous TT-G haplotype (homeostatic model assessment of insulin resistance: 3.4+/-0.4 vs. 5.6+/-0.7 mmol/l, P=0.001; fasting insulin: 86.6+/-11.9 vs. 128.8+/-16.5 pmol/l, P=0.003; BMI: 29.3+/-1.2 vs. 33.9+/-1.3 kg/m, P=0.002). No association with BMI was found in healthy women. CONCLUSION: G(-168)A is functionally relevant and in linkage with TT(-695/-694)GC. GNAQ promoter diplotypes are associated with insulin resistance and obesity in PCOS.