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https://www.readbyqxmd.com/read/28642345/evolution-of-nonspectral-rhodopsin-function-at-high-altitudes
#1
Gianni M Castiglione, Frances E Hauser, Brian S Liao, Nathan K Lujan, Alexander Van Nynatten, James M Morrow, Ryan K Schott, Nihar Bhattacharyya, Sarah Z Dungan, Belinda S W Chang
High-altitude environments present a range of biochemical and physiological challenges for organisms through decreases in oxygen, pressure, and temperature relative to lowland habitats. Protein-level adaptations to hypoxic high-altitude conditions have been identified in multiple terrestrial endotherms; however, comparable adaptations in aquatic ectotherms, such as fishes, have not been as extensively characterized. In enzyme proteins, cold adaptation is attained through functional trade-offs between stability and activity, often mediated by substitutions outside the active site...
June 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28641980/cardiomyocyte-specific-overexpression-of-a-37-amino-acid-domain-of-regulator-of-g-protein-signalling-2-inhibits-cardiac-hypertrophy-and-improves-function-in-response-to-pressure-overload-in-mice
#2
Katherine N Lee, Xiangru Lu, Chau Nguyen, Qingping Feng, Peter Chidiac
Regulator of G protein signalling 2 (RGS2) is known to play a protective role in maladaptive cardiac hypertrophy and heart failure via its ability to inhibit Gq and Gs mediated GPCR signalling. We previously demonstrated that RGS2 can also inhibit protein translation and can thereby attenuate cell growth. This G protein-independent inhibitory effect has been mapped to a 37 amino acid domain (RGS2(eb)) within RGS2 that binds to eukaryotic initiation factor 2B (eIF2B). When expressed in neonatal rat cardiomyocytes, RGS2(eb) attenuates both protein synthesis and hypertrophy induced by Gq- and Gs- activating agents...
June 19, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28641070/elmo-proteins-transduce-g-protein-coupled-receptor-signal-to-control-reorganization-of-actin-cytoskeleton-in-chemotaxis-of-eukaryotic-cells
#3
Xuehua Xu, Tian Jin
Chemotaxis, which is chemoattractant-guided directional cell migration, plays major roles in recruitment of neutrophils, the metastasis of cancer cells, and the development of the model organism Dictyostelium discoideum. These cells share remarkable similarities in the signaling pathways by which they control chemotaxis. They all use a G protein-coupled receptor (GPCR)-mediated signal transduction pathway to sense the chemotactic gradient to guide cell migration. Diverse chemokines activate Rac through conserved GPCR signaling pathways...
June 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28634209/genetic-evidence-that-%C3%AE-arrestins-are-dispensable-for-the-initiation-of-%C3%AE-2-adrenergic-receptor-signaling-to-erk
#4
Morgan O'Hayre, Kelsie Eichel, Silvia Avino, Xuefeng Zhao, Dana J Steffen, Xiaodong Feng, Kouki Kawakami, Junken Aoki, Karen Messer, Roger Sunahara, Asuka Inoue, Mark von Zastrow, J Silvio Gutkind
The β2-adrenergic receptor (β2AR) has provided a paradigm to elucidate how G protein-coupled receptors (GPCRs) control intracellular signaling, including the discovery that β-arrestins, which bind to ligand-activated GPCRs, are central for GPCR function. We used genome editing, conditional gene deletion, and small interfering RNAs (siRNAs) to determine the roles of β-arrestin 1 (β-arr1) and β-arr2 in β2AR internalization, trafficking, and signaling to ERK. We found that only β-arr2 was essential for β2AR internalization...
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28626925/stoichiometric-analysis-of-oligomeric-states-of-three-class-a-gpcrs-chemokine-cxcr4-dopamine-d2-and-prostaglandin-ep1-receptors-on-living-cells
#5
Kenichi Kawano, Tetsuya Yagi, Nozomu Fukada, Yoshiaki Yano, Katsumi Matsuzaki
G-protein-coupled receptors (GPCRs) form the largest family of transmembrane receptors, and their oligomerization has been suggested to be related to their functions. Despite extensive studies, their oligomeric states are highly controversial. One of the reasons is the overestimation of oligomerization by conventional methods. We recently established a stoichiometric analysis method for precisely determining the oligomeric state of membrane proteins on living cells with the combined use of the coiled-coil labeling method and a spectral imaging technique and showed that the prototypical class-A GPCR β2 -adrenergic receptor (β2 AR) did not form functional oligomers...
June 18, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28626043/the-diverse-roles-of-arrestin-scaffolds-in-g-protein-coupled-receptor-signaling
#6
REVIEW
Yuri K Peterson, Louis M Luttrell
The visual/β-arrestins, a small family of proteins originally described for their role in the desensitization and intracellular trafficking of G protein-coupled receptors (GPCRs), have emerged as key regulators of multiple signaling pathways. Evolutionarily related to a larger group of regulatory scaffolds that share a common arrestin fold, the visual/β-arrestins acquired the capacity to detect and bind activated GPCRs on the plasma membrane, which enables them to control GPCR desensitization, internalization, and intracellular trafficking...
July 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28623260/qualifying-a-eukaryotic-cell-free-system-for-fluorescence-based-gpcr-analyses
#7
Anne Zemella, Solveig Grossmann, Rita Sachse, Andrei Sonnabend, Michael Schaefer, Stefan Kubick
Membrane proteins are key elements in cell-mediated processes. In particular, G protein-coupled receptors (GPCRs) have attracted increasing interest since they affect cellular signaling. Furthermore, mutations in GPCRs can cause acquired and inheritable diseases. Up to date, there still exist a number of GPCRs that has not been structurally and functionally analyzed due to difficulties in cell-based membrane protein production. A promising approach for membrane protein synthesis and analysis has emerged during the last years and is known as cell-free protein synthesis (CFPS)...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619258/rho-kinase-dependent-desensitization-of-gpr39-a-unique-mechanism-of-gpcr-downregulation
#8
Yuji Shimizu, Ryokichi Koyama, Tomohiro Kawamoto
GPR39, a G-protein-coupled receptor activated by zinc, reportedly activates multiple intracellular signaling pathways via Gs, Gq, G12/13, and β-arrestin, but little is known about downregulation of the receptor upon its activation. To our knowledge, this is the first report on the mechanism of feedback regulation of GPR39 function determined in GPR39-expressing HEK293 cells (HEK293-GPR39) as a model cell system. In HEK293-GPR39 cells, GPR39-C3, which is a positive allosteric modulator, activated cAMP production (downstream of Gs), IP1 accumulation (downstream of Gq), SRF-RE-dependent transcription (downstream of G12/13), and β-arrestin recruitment...
June 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28618224/design-synthesis-and-structure-activity-relationship-of-tetrahydropyrido-4-3-d-pyrimidine-derivatives-as-potent-smoothened-antagonists-with-in-vivo-activity
#9
Wenfeng Lu, Yongqiang Liu, Haikuo Ma, Jiyue Zheng, Sheng Tian, Zhijian Sun, Lusong Luo, Jiajun Li, Hongjian Zhang, Zeng-Jie Yang, Xiaohu Zhang
Medulloblastoma is one of the most prevalent brain tumors in children. Aberrant hedgehog (Hh) pathway signaling is thought to be involved in the initiation and development of medulloblastoma. Vismodegib, the first FDA-approved cancer therapy based on inhibition of aberrant hedgehog signaling, targets smoothened (Smo), a G-protein coupled receptor (GPCR) central to the Hh pathway. Although vismodegib exhibits promising therapeutic efficacy in tumor treatment, concerns have been raised from its non-linear pharmacokinetic (PK) profiles at high doses partly due to low aqueous solubility...
June 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28615442/the-heterotrimeric-g-protein-g%C3%AE-1-interacts-with-the-catalytic-subunit-of-protein-phosphatase-1-and-modulates-g-protein-coupled-receptor-signaling-in-platelets
#10
Subhashree Pradhan, Tanvir Khatlani, Angus C Nairn, K Vinod Vijayan
Thrombosis is caused by the activation of platelets at the site of ruptured atherosclerotic plaques. This activation involves engagement of G protein coupled receptors (GPCR) on platelets that promotes their aggregation. Although it is known that protein kinases and phosphatases modulate GPCR signaling, how serine/threonine phosphatases integrate with G protein signaling pathways is less understood. Since the subcellular localization and substrate specificity of the catalytic subunit of protein phosphatase 1 (PP1c) is dictated by PP1c-interacting proteins, here we sought to identify new PP1c interactors...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615320/differential-phosphorylation-signals-control-endocytosis-of-gpr15
#11
Yukari Okamoto, Sojin Shikano
GPR15 is an orphan G protein-coupled receptor (GPCR) that serves for an HIV coreceptor and was also recently found as a novel homing receptor for T cells implicated in colitis. We show that GPR15 undergoes a constitutive endocytosis in the absence of ligand. The endocytosis was clathrin-dependent and partially dependent on β-arrestin in HEK293 cells, and nearly half of the internalized GPR15 receptors were recycled to the plasma membrane. Ala mutation of the distal C-terminal Arg(354) or Ser(357), which forms a consensus phosphorylation site for basophilic kinases, markedly reduced the endocytosis while phosphomimetic mutation of Ser(357) to Asp did not...
June 14, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28613457/live-cell-imaging-of-cell-signaling-using-genetically-encoded-fluorescent-reporters
#12
REVIEW
Qiang Ni, Sohum Mehta, Jin Zhang
Synergistic advances in fluorescent protein (FP) engineering and live-cell imaging techniques in recent years have fueled the concurrent development and application of genetically encoded fluorescent reporters that are tailored for tracking signaling dynamics in living systems over multiple length and time scales. These biosensors are uniquely suited for this challenging task, owing to their specificity, sensitivity, and versatility, as well as to the non-invasive and non-destructive nature of fluorescence and the power of genetic encoding...
June 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28611581/glial-endozepines-inhibit-feeding-related-autonomic-functions-by-acting-at-the-brainstem-level
#13
Florent Guillebaud, Clémence Girardet, Anne Abysique, Stéphanie Gaigé, Rym Barbouche, Jérémy Verneuil, André Jean, Jérôme Leprince, Marie-Christine Tonon, Michel Dallaporta, Bruno Lebrun, Jean-Denis Troadec
Endozepines are endogenous ligands for the benzodiazepine receptors and also target a still unidentified GPCR. The endozepine octadecaneuropeptide (ODN), an endoproteolytic processing product of the diazepam-binding inhibitor (DBI) was recently shown to be involved in food intake control as an anorexigenic factor through ODN-GPCR signaling and mobilization of the melanocortinergic signaling pathway. Within the hypothalamus, the DBI gene is mainly expressed by non-neuronal cells such as ependymocytes, tanycytes, and protoplasmic astrocytes, at levels depending on the nutritional status...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28611180/papers-of-note-in-nature546-7657
#14
Annalisa M VanHook
This week's articles highlight an unusual mechanism for switching off GPCR signaling; the structural basis of activation of the GLP-1 receptor; a critical role for the B cell receptor in some lymphoma cells; and how cancer cells exploit nutrient sensing and acquisition pathways.
June 13, 2017: Science Signaling
https://www.readbyqxmd.com/read/28609587/chemogenetic-modulation-of-g-protein-coupled-receptor-signalling-in-visual-attention-research
#15
Søren H Jørgensen, Ciarán Martin Fitzpatrick, Ulrik Gether, David D P Woldbye, Andreas T Sørensen
Attention is a fundamental cognitive process involved in nearly all aspects of life. Abnormal attention control is a symptom of many neurological disorders, most notably recognized in ADHD (attention deficit hyperactivity disorder). Although attentional performance and its malfunction has been a major area of investigation, it has proven difficult to accurately associate specific neuronal projections, cell types, neurotransmitter systems and receptors with distinct phenotypes owing to its complexity. In this MiniReview, we present a recently invented technology known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)...
June 13, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28609478/purification-of-family-b-g-protein-coupled-receptors-using-nanodiscs-application-to-human-glucagon-like-peptide-1-receptor
#16
Yingying Cai, Yuting Liu, Kelly J Culhane, Brian T DeVree, Yang Yang, Roger K Sunahara, Elsa C Y Yan
Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e...
2017: PloS One
https://www.readbyqxmd.com/read/28607487/single-molecule-analysis-of-ligand-efficacy-in-%C3%AE-2ar-g-protein-activation
#17
G Glenn Gregorio, Matthieu Masureel, Daniel Hilger, Daniel S Terry, Manuel Juette, Hong Zhao, Zhou Zhou, Jose Manuel Perez-Aguilar, Maria Hauge, Signe Mathiasen, Jonathan A Javitch, Harel Weinstein, Brian K Kobilka, Scott C Blanchard
G-protein-coupled receptor (GPCR)-mediated signal transduction is central to human physiology and disease intervention, yet the molecular mechanisms responsible for ligand-dependent signalling responses remain poorly understood. In class A GPCRs, receptor activation and G-protein coupling entail outward movements of transmembrane helix 6 (TM6). Here, using single-molecule fluorescence resonance energy transfer imaging, we examine TM6 movements in the β2 adrenergic receptor (β2AR) upon exposure to orthosteric ligands with different efficacies, in the absence and presence of the Gs heterotrimer...
June 7, 2017: Nature
https://www.readbyqxmd.com/read/28603493/role-of-atypical-chemokine-receptors-in-microglial-activation-and-polarization
#18
REVIEW
Valentina Salvi, Francesca Sozio, Silvano Sozzani, Annalisa Del Prete
Inflammatory reactions occurring in the central nervous system (CNS), known as neuroinflammation, are key components of the pathogenic mechanisms underlying several neurological diseases. The chemokine system plays a crucial role in the recruitment and activation of immune and non-immune cells in the brain, as well as in the regulation of microglia phenotype and function. Chemokines belong to a heterogeneous family of chemotactic agonists that signal through the interaction with G protein-coupled receptors (GPCRs)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28600358/cell-adhesion-controlled-by-adhesion-g-protein-coupled-receptor-gpr124-adgra2-is-mediated-by-a-protein-complex-comprising-intersectins-and-elmo-dock
#19
Magda Nohemí Hernández-Vásquez, Sendi Rafael Adame-García, Noumeira Hamoud, Rony Chidiac, Guadalupe Reyes-Cruz, Jean Philippe Gratton, Jean-François Côté, José Vázquez-Prado
Developmental angiogenesis and the maintenance of blood brain barrier involve endothelial cell adhesion, which are linked to cytoskeletal dynamics. GPR124 (also known as TEM5/ADGRA2) is an Adhesion GPCR-family member that plays a pivotal role in brain angiogenesis and in ensuring a tight blood-brain barrier. However, the signaling properties of GPR124 remain poorly defined. Here, we show that ectopic expression of GPR124 promotes cell adhesion, additive to extracellular matrix-dependent effect, coupled with filopodia and lamellipodia formation and an enrichment of a pool of the GPCR at actin-rich cellular protrusions containing VASP, a filopodial marker...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28591604/g-protein-coupled-receptors-contain-two-conserved-packing-clusters
#20
Omar B Sanchez-Reyes, Aidan L G Cooke, Dale B Tranter, Dawood Rashid, Markus Eilers, Philip J Reeves, Steven O Smith
G protein-coupled receptors (GPCRs) have evolved a seven-transmembrane helix framework that is responsive to a wide range of extracellular signals. An analysis of the interior packing of family A GPCR crystal structures reveals two clusters of highly packed residues that facilitate tight transmembrane helix association. These clusters are centered on amino acid positions 2.47 and 4.53, which are highly conserved as alanine and serine, respectively. Ala2.47 mediates the interaction between helices H1 and H2, while Ser4...
June 6, 2017: Biophysical Journal
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