Genome-wide prediction of G protein-coupled receptors in Verticillium spp.

TLQP-21, a peptide derived from VGF (non-acronymic) by proteolytic processing, has been shown to modulate energy metabolism, differentiation, and cellular response to stress. Although extensively investigated, the receptor for this endogenous peptide has not previously been described. This study describes the use of a series of studies that show G protein-coupled receptor-mediated biological activity of TLQP-21 signaling in CHO-K1 cells. Unbiased genome-wide sequencing of the transcriptome from responsive CHO-K1 cells identified a prioritized list of possible G protein-coupled receptors bringing about this activity. Further experiments using a series of defined receptor antagonists and siRNAs led to the identification of complement C3a receptor-1 (C3AR1) as a target for TLQP-21 in rodents. We have not been able to demonstrate so far that this finding is translatable to the human receptor. Our results are in line with a large number of physiological observations in rodent models of food intake and metabolic control, where TLQP-21 shows activity. In addition, the sensitivity of TLQP-21 signaling to pertussis toxin is consistent with the known signaling pathway of C3AR1. The binding of TLQP-21 to C3AR1 not only has effects on signaling but also modulates cellular functions, as TLQP-21 was shown to have a role in directing migration of mouse RAW264.7 cells.

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A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors

Molecular Cell ◽

10.1016/j.molcel.2012.10.018 ◽

2013 ◽

Vol 49 (1) ◽

pp. 94-108 ◽

Cited By ~ 86

Author(s):

Jose P. Vaqué ◽

Robert T. Dorsam ◽

Xiaodong Feng ◽

Ramiro Iglesias-Bartolome ◽

David J. Forsthoefel ◽

...

Keyword(s):

G Protein ◽

Rho Gtpase ◽

Rnai Screen ◽

G Protein Coupled Receptors ◽

Genome Wide ◽

A Genome ◽

G Protein Coupled ◽

Mitogenic Signals

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Orphan G Protein Coupled Receptors in Affective Disorders

Genes ◽

10.3390/genes11060694 ◽

2020 ◽

Vol 11 (6) ◽

pp. 694 ◽

Cited By ~ 3

Author(s):

Lyndsay R. Watkins ◽

Cesare Orlandi

Keyword(s):

G Protein ◽

Animal Studies ◽

Association Studies ◽

G Protein Coupled Receptors ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Pharmacological Targets ◽

The Central Nervous System ◽

Orphan Gpcrs ◽

G Protein Coupled

G protein coupled receptors (GPCRs) are the main mediators of signal transduction in the central nervous system. Therefore, it is not surprising that many GPCRs have long been investigated for their role in the development of anxiety and mood disorders, as well as in the mechanism of action of antidepressant therapies. Importantly, the endogenous ligands for a large group of GPCRs have not yet been identified and are therefore known as orphan GPCRs (oGPCRs). Nonetheless, growing evidence from animal studies, together with genome wide association studies (GWAS) and post-mortem transcriptomic analysis in patients, pointed at many oGPCRs as potential pharmacological targets. Among these discoveries, we summarize in this review how emotional behaviors are modulated by the following oGPCRs: ADGRB2 (BAI2), ADGRG1 (GPR56), GPR3, GPR26, GPR37, GPR50, GPR52, GPR61, GPR62, GPR88, GPR135, GPR158, and GPRC5B.

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