scholarly journals Membrane progesterone receptor induces meiosis in Xenopus oocytes through endocytosis into signaling endosomes and interaction with APPL1 and Akt2

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000901
Author(s):  
Nancy Nader ◽  
Maya Dib ◽  
Rawad Hodeify ◽  
Raphael Courjaret ◽  
Asha Elmi ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Xenopus Oocytes ◽  
Steroid Hormone ◽  
Adaptor Protein ◽  
G Protein Coupled Receptors ◽  
Adiponectin Receptors ◽  
Physiological Processes ◽  
Oocyte Meiosis ◽  
Membrane Progesterone Receptor ◽  
G Protein Coupled

The steroid hormone progesterone (P4) mediates many physiological processes through either nuclear receptors that modulate gene expression or membrane P4 receptors (mPRs) that mediate nongenomic signaling. mPR signaling remains poorly understood. Here we show that the topology of mPRβ is similar to adiponectin receptors and opposite to that of G-protein-coupled receptors (GPCRs). Using Xenopus oocyte meiosis as a well-established physiological readout of nongenomic P4 signaling, we demonstrate that mPRβ signaling requires the adaptor protein APPL1 and the kinase Akt2. We further show that P4 induces clathrin-dependent endocytosis of mPRβ into signaling endosome, where mPR interacts transiently with APPL1 and Akt2 to induce meiosis. Our findings outline the early steps involved in mPR signaling and expand the spectrum of mPR signaling through the multitude of pathways involving APPL1.

Compartmentalization of GPCR signalling controls unique cellular responses

2016 ◽  
Vol 44 (2) ◽  
pp. 562-567 ◽  
Author(s):  
Andrew M. Ellisdon ◽  
Michelle L. Halls
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Attrition Rates ◽  
Physiological Processes ◽  
Simple Chain ◽  
G Protein Coupled ◽  
Major Drug ◽  
Very High

With >800 members, G protein-coupled receptors (GPCRs) are the largest class of cell-surface signalling proteins, and their activation mediates diverse physiological processes. GPCRs are ubiquitously distributed across all cell types, involved in many diseases and are major drug targets. However, GPCR drug discovery is still characterized by very high attrition rates. New avenues for GPCR drug discovery may be provided by a recent shift away from the traditional view of signal transduction as a simple chain of events initiated from the plasma membrane. It is now apparent that GPCR signalling is restricted to highly organized compartments within the cell, and that GPCRs activate distinct signalling pathways once internalized. A high-resolution understanding of how compartmentalized signalling is controlled will probably provide unique opportunities to selectively and therapeutically target GPCRs.

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

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.

Identification Methods of G Protein-Coupled Receptors

2011 ◽  
Vol 2 (4) ◽  
pp. 35-52
Author(s):  
Meriem Zekri ◽  
Karima Alem ◽  
Labiba Souici-Meslati
Keyword(s):  
Immune Responses ◽  
G Protein ◽  
Pharmaceutical Research ◽  
G Protein Coupled Receptors ◽  
Machine Learning Algorithms ◽  
Signaling Networks ◽  
Identification Methods ◽  
Physiological Processes ◽  
Cell Signaling Networks ◽  
G Protein Coupled

The G protein-coupled receptors (GPCRs) include one of the largest and most important families of multifunctional proteins known to molecular biology. They play a key role in cell signaling networks that regulate many physiological processes, such as vision, smell, taste, neurotransmission, secretion, immune responses, metabolism, and cell growth. These proteins are thus very important for understanding human physiology and they are involved in several diseases. Therefore, many efforts in pharmaceutical research are to understand their structures and functions, which is not an easy task, because although thousands GPCR sequences are known, many of them remain orphans. To remedy this, many methods have been developed using methods such as statistics, machine learning algorithms, and bio-inspired approaches. In this article, the authors review the approaches used to develop algorithms for classification GPCRs by trying to highlight the strengths and weaknesses of these different approaches and providing a comparison of their performances.

scholarly journals Characterization and Expression Profiling of Neuropeptides and G-Protein-Coupled Receptors (GPCRs) for Neuropeptides in the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Psyllidae)

2018 ◽  
Vol 19 (12) ◽  
pp. 3912 ◽  
Author(s):  
Zhengbing Wang ◽  
Wenwu Zhou ◽  
Muhammad Hameed ◽  
Jiali Liu ◽  
Xinnian Zeng
Keyword(s):  
G Protein ◽  
Developmental Stages ◽  
G Protein Coupled Receptors ◽  
Nerve Tissue ◽  
Asian Citrus Psyllid ◽  
Diaphorina Citri ◽  
Physiological Processes ◽  
Neuropeptide Receptors ◽  
G Protein Coupled ◽  
Active Substances

Neuropeptides are endogenous active substances that widely exist in multicellular biological nerve tissue and participate in the function of the nervous system, and most of them act on neuropeptide receptors. In insects, neuropeptides and their receptors play important roles in controlling a multitude of physiological processes. In this project, we sequenced the transcriptome from twelve tissues of the Asian citrus psyllid, Diaphorina citri Kuwayama. A total of 40 candidate neuropeptide genes and 42 neuropeptide receptor genes were identified. Among the neuropeptide receptor genes, 35 of them belong to the A-family (or rhodopsin-like), four of them belong to the B-family (or secretin-like), and three of them are leucine-rich repeat-containing G-protein-coupled receptors. The expression profile of the 82 genes across developmental stages was determined by qRT-PCR. Our study provides the first investigation on the genes of neuropeptides and their receptors in D. citri, which may play key roles in regulating the physiology and behaviors of D. citri.

G-Protein-Coupled Receptors in Drug Discovery: Nanosizing Using Cell-Free Technologies and Molecular Biology Approaches

2005 ◽  
Vol 10 (8) ◽  
pp. 765-779 ◽  
Author(s):  
Wayne R. Leifert ◽  
Amanda L. Aloia ◽  
Olgatina Bucco ◽  
Richard V. Glatz ◽  
Edward J. McMurchie
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Drug Targets ◽  
G Protein Coupled Receptors ◽  
Orphan Receptors ◽  
Molecular Switching ◽  
Physiological Processes ◽  
Current Cell ◽  
G Protein Coupled ◽  
Signaling Components

Signal transduction by G-protein-coupled receptors (GPCRs) underpins a multitude of physiological processes. Ligand recognition by the receptor leads to activation of a genericmolecular switch involving heterotrimeric G-proteins and guanine nucleotides. Signal transduction has been studied extensively with both cell-based systems and assays comprising isolated signaling components. Interest and commercial investment in GPCRs in areas such as drug targets, orphan receptors, highthroughput screening, biosensors, and so on will focus greater attention on assay development to allow for miniaturization, ultra-high throughput and, eventually, microarray/biochip assay formats. Although cell-based assays are adequate for many GPCRs, it is likely that these formatswill limit the development of higher density GPCRassay platforms mandatory for other applications. Stable, robust, cell-free signaling assemblies comprising receptor and appropriate molecular switching components will form the basis of future GPCR assay platforms adaptable for such applications as microarrays. The authors review current cell-free GPCR assay technologies and molecular biological approaches for construction of novel, functional GPCR assays.

scholarly journals G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiao-Fan Zhao
Keyword(s):  
Cell Membrane ◽  
Steroid Hormones ◽  
G Protein ◽  
Steroid Hormone ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Research Progress ◽  
Nongenomic Action ◽  
Signaling Axis ◽  
G Protein Coupled

Abstract G protein-coupled receptors (GPCRs) are cell membrane receptors for various ligands. Recent studies have suggested that GPCRs transmit animal steroid hormone signals. Certain GPCRs have been shown to bind steroid hormones, for example, G protein-coupled estrogen receptor 1 (GPER1) binds estrogen in humans, and Drosophila dopamine/ecdysteroid receptor (DopEcR) binds the molting hormone 20-hydroxyecdysone (20E) in insects. This review summarizes the research progress on GPCRs as animal steroid hormone cell membrane receptors, including the nuclear and cell membrane receptors of steroid hormones in mammals and insects, the 20E signaling cascade via GPCRs, termination of 20E signaling, and the relationship between genomic action and the nongenomic action of 20E. Studies indicate that 20E induces a signal via GPCRs to regulate rapid cellular responses, including rapid Ca2+ release from the endoplasmic reticulum and influx from the extracellular medium, as well as rapid protein phosphorylation and subcellular translocation. 20E via the GPCR/Ca2+/PKC/signaling axis and the GPCR/cAMP/PKA-signaling axis regulates gene transcription by adjusting transcription complex formation and DNA binding activity. GPCRs can bind 20E in the cell membrane and after being isolated, suggesting GPCRs as cell membrane receptors of 20E. This review deepens our understanding of GPCRs as steroid hormone cell membrane receptors and the GPCR-mediated signaling pathway of 20E (20E-GPCR pathway), which will promote further study of steroid hormone signaling via GPCRs, and presents GPCRs as targets to explore new pharmaceutical materials to treat steroid hormone-related diseases or control pest insects. Graphical abstract

scholarly journals Serotonin GPCR-based biosensing modalities in yeast

2021 ◽  
Author(s):  
Bettina Lengger ◽  
Emma E. Hoch-Schneider ◽  
Christina Noerskov ◽  
Tadas Jakociunas ◽  
Emil D. Jensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
G Proteins ◽  
Reporter Gene ◽  
G Protein Coupled Receptors ◽  
Human Populations ◽  
Physiological Processes ◽  
G Protein Coupled ◽  
Health Applications

Serotonin is a key neurotransmitter involved in numerous physiological processes and serves as an important precursor for manufacturing bioactive indoleamines and alkaloids used in the treatment of human pathologies. In humans, serotonin sensing and signaling can occur by 12 G protein-coupled receptors (GPCRs) coupled to G proteins. To systematically assess serotonin GPCR signaling, we characterized reporter gene expression of a 144-sized library encoding all 12 human serotonin GPCRs in combination with 12 different Gα proteins in yeast exposed to serotonin. For the 5-HT4 receptor, we observe 25- and 64-fold changes in EC50 values and dynamic reporter gene outputs, respectively. Furthermore, we show that optimal biosensing designs enable high-resolution sensing of serotonin produced in yeast, as well as provide a platform for characterization of 19 serotonin GPCR polymorphisms found in human populations. Taken together, our study highlights serotonin biosensing modalities of relevance to both biotechnological and human health applications.

scholarly journals Serial Femtosecond Crystallography of G Protein–Coupled Receptors

2018 ◽  
Vol 47 (1) ◽  
pp. 377-397 ◽  
Author(s):  
Benjamin Stauch ◽  
Vadim Cherezov
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
Structural Studies ◽  
Body Structure ◽  
X Ray ◽  
Physiological Processes ◽  
Recent Emergence ◽  
Mediate Cell ◽  
G Protein Coupled ◽  
Serial Femtosecond Crystallography

G protein–coupled receptors (GPCRs) represent a large superfamily of membrane proteins that mediate cell signaling and regulate a variety of physiological processes in the human body. Structure-function studies of this superfamily were enabled a decade ago by multiple breakthroughs in technology that included receptor stabilization, crystallization in a membrane environment, and microcrystallography. The recent emergence of X-ray free-electron lasers (XFELs) has further accelerated structural studies of GPCRs and other challenging proteins by overcoming radiation damage and providing access to high-resolution structures and dynamics using micrometer-sized crystals. Here, we summarize key technology advancements and major milestones of GPCR research using XFELs and provide a brief outlook on future developments in the field.

scholarly journals International Union of Basic and Clinical Pharmacology. Recommendations for GPCR ligand bias

2021 ◽  
Author(s):  
Peter Kolb et al. ◽  
David Gloriam
Keyword(s):  
Cellular Tissue ◽  
G Protein Coupled Receptors ◽  
Physiological Processes ◽  
Biased Signaling ◽  
Receptor Research ◽  
Approved Drugs ◽  
Ligand Bias ◽  
G Protein Coupled ◽  
Fda Approved Drugs ◽  
Common Understanding

G protein-coupled receptors modulate a plethora of physiological processes and mediate the effects of one-third of FDA-approved drugs. Notably, depending on which ligand has activated a particular receptor, it can engage different intracellular transducers. This paradigm of ligand-dependent ‘biased signaling’ dictates a need to advance beyond the level of receptors to consider the combined ligand-receptor pair in order to understand physiological signaling. Bias signaling also has the potential to improve medicines by reducing adverse effects. However, this is challenged by inconsistent interpretation of results and lack of commonly agreed guidelines. Here, we present recommended terminology and guidelines to conduct, report and quantify bias in a comparable and reproducible fashion. We expect these recommendations will facilitate a common understanding of experiments and findings across basic receptor research and drug discovery, while the area and the analytical methods to measure bias are still evolving, especially in complex cellular, tissue and organismal systems.

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