The G protein-coupled receptor repertoires of human and mouse

Vassilatis, Demetrios K.; Hohmann, John G.; Zeng, Hongkui; Li, Fusheng; Ranchalis, Jane; Mortrud, Marty; Brown, Analisa; Rodriguez, Stephanie S.; Weller, John R.; Wright, Abbie C.; Bergmann, John E.; Gaitanaris, George A.

doi:10.1073/pnas.0230374100

Cited by 667 publications

(506 citation statements)

References 39 publications

Supporting

Mentioning

488

Contrasting

Unclassified

Order By: Relevance

“…The brain expresses about 90% of all known GPCRs (Vassilatis et al . 2003; Premont & Gainetdinov, 2007), and the majority of them recognize diverse physiological, signals such as hormones, neurotransmitters, ions, peptides, lipids and cellular metabolites, and convert them into a variety of meaningful cellular signals. Briefly, ligand binding to the extracellular portion of GPCRs structurally alters their intracellular domain allowing them to function as guanine nucleotide exchange factors for heterotrimeric guanine nucleotide‐binding proteins (G proteins).…”

Section: Gpcr Modulation: a Brief Overviewmentioning

confidence: 99%

Regulation of neuronal chloride homeostasis by neuromodulators

Mahadevan

Woodin

2016

The Journal of Physiology

View full text Add to dashboard Cite

KCC2 is the central regulator of neuronal Cl− homeostasis, and is critical for enabling strong hyperpolarizing synaptic inhibition in the mature brain. KCC2 hypofunction results in decreased inhibition and increased network hyperexcitability that underlies numerous disease states including epilepsy, neuropathic pain and neuropsychiatric disorders. The current holy grail of KCC2 biology is to identify how we can rescue KCC2 hypofunction in order to restore physiological levels of synaptic inhibition and neuronal network activity. It is becoming increasingly clear that diverse cellular signals regulate KCC2 surface expression and function including neurotransmitters and neuromodulators. In the present review we explore the existing evidence that G‐protein‐coupled receptor (GPCR) signalling can regulate KCC2 activity in numerous regions of the nervous system including the hypothalamus, hippocampus and spinal cord. We present key evidence from the literature suggesting that GPCR signalling is a conserved mechanism for regulating chloride homeostasis. This evidence includes: (1) the activation of group 1 metabotropic glutamate receptors and metabotropic Zn2+ receptors strengthens GABAergic inhibition in CA3 pyramidal neurons through a regulation of KCC2; (2) activation of the 5‐hydroxytryptamine type 2A serotonin receptors upregulates KCC2 cell surface expression and function, restores endogenous inhibition in motoneurons, and reduces spasticity in rats; and (3) activation of A3A‐type adenosine receptors rescues KCC2 dysfunction and reverses allodynia in a model of neuropathic pain. We propose that GPCR‐signals are novel endogenous Cl− extrusion enhancers that may regulate KCC2 function.

show abstract

Section: Gpcr Modulation: a Brief Overviewmentioning

confidence: 99%

Regulation of neuronal chloride homeostasis by neuromodulators

Mahadevan

Woodin

2016

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…Moreover, many of these studies, and indeed studies on the general evolution of the Rhodopsin-like family, have examined very narrow species distributions, for instance specifically teleosts (Gloriam et al, 2005), primates (Anbazhagan et al, 2010), humans and mice (Vassilatis et al, 2003;Kakarala and Jamil, 2014), or even strictly humans (Fredriksson et al, 2003). Thus, virtually no studies accounting for the full breadth of vertebrate bioamine receptor sequences have been conducted.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive, structurally-curated alignment and phylogeny of vertebrate biogenic amine receptors

Spielman

Kumar

Wilke

2014

Preprint

View full text Add to dashboard Cite

Biogenic amine receptors play critical roles in regulating behavior and physiology, particularly within the central nervous system, in both vertebrates and invertebrates. These receptors belong to the G-protein coupled receptor (GPCR) family and interact with endogenous bioamine ligands, such as dopamine, serotonin, and epinephrine, and they are targeted by a wide array of pharmaceuticals. Despite these receptors' clear clinical and biological importance, their evolutionary history remains poorly characterized. In particular, the relationships among biogenic amine receptors and any specific evolutionary constraints acting within distinct receptor subtypes are largely unknown. To advance and facilitate studies in this receptor family, we have constructed a comprehensive, high-quality, structurally-curated sequence alignment of vertebrate biogenic amine receptors. We demonstrate that aligning GPCR sequences without considering structure produces an alignment with substantial error, whereas a structurally-aware approach greatly improves alignment accuracy. Moreover, we show that phylogenetic inference with our structurally-curated alignment offers dramatic improvements over a structurally-naive alignment. Using the structural alignment and its corresponding phylogeny, we deduce novel biogenic amine receptor relationships and uncover previously unrecognized lineage-specific receptor clades. Moreover, we find that roughly 1% of the 3039 sequences in our final alignment are either misannotated or unclassified, and we propose updated classifications for these receptors. We release our comprehensive alignment and its corresponding phylogeny as a resource for future research into the evolution and diversification of biogenic amine receptors.

show abstract

“…Many GPCRs exist. In fact, the GPCR superfamily is the largest class of cell surface receptors and almost 1,000 GPCRs are thought to be encoded by the human genome (Fredriksson & Schioth, 2005;Perez, 2003, Takeda et al, 2002Vassilatis et al, 2003). These receptors have diverse roles in that they regulate overall organism homeostasis as well as embryo development, and they are also involved in learning, memory, vision, smell and taste.…”

Section: Introductionmentioning

confidence: 99%

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Winzell

Åhrén

2007

Pharmacology & Therapeutics

163

View full text Add to dashboard Cite

Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanine nucleotide-binding protein (G-protein) coupled receptors (GPCRs). Examples of islet GPCRs are GPR40 and GPR119, which are GPCRs with fatty acids as ligands, the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the receptors for the islet hormones glucagon and somatostatin, the receptors for the classical neurotransmittors

show abstract

The G protein-coupled receptor repertoires of human and mouse

Cited by 667 publications

References 39 publications

Regulation of neuronal chloride homeostasis by neuromodulators

Regulation of neuronal chloride homeostasis by neuromodulators

Comprehensive, structurally-curated alignment and phylogeny of vertebrate biogenic amine receptors

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Contact Info

Product

Resources

About