Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep

The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G-Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network. Single cell sequencing indicates that they are not only differentially expressed but also define clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy with a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a novel role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.

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Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

Journal of Pathogens ◽

10.1155/2018/9541987 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Neil N. Patel ◽

Alan D. Workman ◽

Noam A. Cohen

Keyword(s):

Airway Epithelium ◽

Taste Receptor ◽

Upper Airway ◽

Airway Disease ◽

G Protein Coupled Receptors ◽

Innate Immune ◽

Taste Receptors ◽

Taste Sensation ◽

G Protein Coupled

Evidence is emerging that shows taste receptors serve functions outside of taste sensation of the tongue. Taste receptors have been found in tissue across the human body, including the gastrointestinal tract, bladder, brain, and airway. These extraoral taste receptors appear to be important in modulating the innate immune response through detection of pathogens. This review discusses taste receptor signaling, focusing on the G-protein–coupled receptors that detect bitter and sweet compounds in the upper airway epithelium. Emphasis is given to recent studies which link the physiology of sinonasal taste receptors to clinical manifestation of upper airway disease.

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The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2018.00179 ◽

2018 ◽

Vol 5 ◽

Cited By ~ 2

Author(s):

Gayathri Viswanathan ◽

Argen Mamazhakypov ◽

Ralph T. Schermuly ◽

Sudarshan Rajagopal

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricle ◽

G Protein ◽

G Protein Coupled Receptors ◽

The Right ◽

G Protein Coupled

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The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

Frontiers in Pharmacology ◽

10.3389/fphar.2021.640441 ◽

2021 ◽

Vol 12 ◽

Author(s):

Roberta Lattanzi ◽

Cinzia Severini ◽

Daniela Maftei ◽

Luciano Saso ◽

Aldo Badiani

Keyword(s):

Pain Perception ◽

G Protein Coupled Receptors ◽

Cellular Processes ◽

Prokineticin 2 ◽

Physiological Processes ◽

Pathological Conditions ◽

Double Function ◽

The Central Nervous System ◽

G Protein Coupled

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

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G protein coupled receptors as allosteric proteins and the role of allosteric modulators

Journal of Receptors and Signal Transduction ◽

10.3109/10799893.2010.503964 ◽

2010 ◽

Vol 30 (5) ◽

pp. 313-321 ◽

Cited By ~ 28

Author(s):

Terry Kenakin

Keyword(s):

G Protein ◽

G Protein Coupled Receptors ◽

Allosteric Modulators ◽

Allosteric Proteins ◽

G Protein Coupled

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The role of membrane curvature elastic stress for function of rhodopsin-like G protein-coupled receptors

Biochimie ◽

10.1016/j.biochi.2014.10.011 ◽

2014 ◽

Vol 107 ◽

pp. 28-32 ◽

Cited By ~ 11

Author(s):

Olivier Soubias ◽

Walter E. Teague ◽

Kirk G. Hines ◽

Klaus Gawrisch

Keyword(s):

G Protein ◽

Elastic Stress ◽

Membrane Curvature ◽

G Protein Coupled Receptors ◽

G Protein Coupled

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A2B Adenosine Receptor and Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20205139 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5139 ◽

Cited By ~ 11

Author(s):

Zhan-Guo Gao ◽

Kenneth A. Jacobson

Keyword(s):

G Proteins ◽

Anticancer Agents ◽

Immune Suppression ◽

Adenosine Receptors ◽

Immune Surveillance ◽

G Protein Coupled Receptors ◽

Normal Tissues ◽

Cancer Tissues ◽

G Protein Coupled

There are four subtypes of adenosine receptors (ARs), named A1, A2A, A2B and A3, all of which are G protein-coupled receptors (GPCRs). Locally produced adenosine is a suppressant in anti-tumor immune surveillance. The A2BAR, coupled to both Gαs and Gαi G proteins, is one of the several GPCRs that are expressed in a significantly higher level in certain cancer tissues, in comparison to adjacent normal tissues. There is growing evidence that the A2BAR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A2BAR antagonists are novel, potentially attractive anticancer agents. Several antagonists targeting A2BAR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A2BAR. We further discuss the role of the A2BAR in the progression of various cancers, and the rationale of using A2BAR antagonists in cancer therapy.

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Atypical Chemokine Receptors in Cardiovascular Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1676988 ◽

2019 ◽

Vol 119 (04) ◽

pp. 534-541 ◽

Cited By ~ 4

Author(s):

Selin Gencer ◽

Emiel van der Vorst ◽

Maria Aslani ◽

Christian Weber ◽

Yvonne Döring ◽

...

Keyword(s):

G Protein ◽

Chemokine Receptors ◽

Cellular Response ◽

Current Knowledge ◽

G Protein Coupled Receptors ◽

Signalling Pathways ◽

Atherosclerosis Development ◽

G Protein Coupled ◽

Precise Role

AbstractInflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.

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The Role of MC1R in Speciation & Phylogeny

The American Biology Teacher ◽

10.1525/abt.2013.75.9.8 ◽

2013 ◽

Vol 75 (9) ◽

pp. 670-676 ◽

Cited By ~ 1

Author(s):

Susan Offner

Keyword(s):

G Protein ◽

Point Mutation ◽

Solomon Island ◽

G Protein Coupled Receptors ◽

Ancestral Population ◽

Mc1r Gene ◽

The Many ◽

Evolutionary Consequences ◽

G Protein Coupled

A point mutation in the MC1R gene, a G-protein-coupled receptor, has been found that could have led to the formation of two subspecies of Solomon Island flycatcher from a single ancestral population. I discuss the many roles that G-protein-coupled receptors play in vertebrate physiology and how one particular point mutation can have enormous evolutionary consequences.

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New thoughts on the role of the βγ subunit in G protein signal transduction

Biochemistry and Cell Biology ◽

10.1139/o00-075 ◽

2000 ◽

Vol 78 (5) ◽

pp. 537-550 ◽

Cited By ~ 1

Author(s):

Barbara Vanderbeld ◽

Gregory M Kelly

Keyword(s):

Signal Transduction ◽

G Protein ◽

G Proteins ◽

G Protein Coupled Receptors ◽

Limited Information ◽

Α Subunit ◽

Downstream Effectors ◽

Receptor Signal ◽

G Protein Coupled

Heterotrimeric G proteins are involved in numerous biological processes, where they mediate signal transduction from agonist-bound G-protein-coupled receptors to a variety of intracellular effector molecules and ion channels. G proteins consist of two signaling moieties: a GTP-bound α subunit and a βγ heterodimer. The βγ dimer, recently credited as a significant modulator of G-protein-mediated cellular responses, is postulated to be a major determinant of signaling fidelity between G-protein-coupled receptors and downstream effectors. In this review we have focused on the role of βγ signaling and have included examples to demonstrate the heterogeneity in the heterodimer composition and its implications in signaling fidelity. We also present an overview of some of the effectors regulated by βγ and draw attention to the fact that, although G proteins and their associated receptors play an instrumental role in development, there is rather limited information on βγ signaling in embryogenesis.Key words: G protein, βγ subunit, G-protein-coupled receptor, signal transduction, adenylyl cyclase.

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