Thus, we investigated the regulatory functions of its β-adrenergic-like octopamine receptor (PxOctβ3) frame (ORF) of PxOctβ3 was phylogenetically analyzed, and the levels of expression of the receptor mRNA were A series of octopamine receptor agonists and antagonists were tested against PxOctβ3. We showed that the receptor is a member of the Octβ3 protein family, and an analysis using quantitative Only metoclopramide and mianserin had significant antagonistic effects on PxOctβ3, whereas yohimbine,

September 2022 "Platelets are well characterized for their indispensable role in primary hemostasis to Platelet α-granules contain microbicidal proteins, chemokines and growth factors, which upon release NETs were also detected in thrombotic lesions in several disease backgrounds, pointing towards a role The negatively charged DNA within NETs provides a procoagulant surface, and in particular NET-derived In this review, we will discuss the interplay between platelets and NETs and the potential of this alliance

PLC activity results in the generation of diacylglycerol and inositol trisphosphate, which are downstream In this article, we describe the signal transduction elements that regulate PLC gene expression.

We investigated the influence of specific inhibitors of G protein-coupled receptors (GPCR), endocytosis We also adopted live cell imaging to monitor the whole intracellular trafficking process of F-Hst1. The inhibitors of GPCR, ERK1/2, phagocytosis, and clathrin-mediated endocytosis (CME) as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake, which was accompanied by the nullification of the We further showed the intracellular trafficking and targeting process of F-Hst1, in which early endosome

Here, we report the crystallographic and cryo-electron microscopy structures of the cannabinoid receptor Through (un)biased molecular dynamics simulations and mutagenesis experiments, we show that TM2 rearrangement

dynamics (MD) simulation studies have shown PI(4,5)P2 interacting with the Glucagon receptor (GCGR), which In this work, we applied MD simulations supported by native mass spectrometry (nMS) to study lipid interactions We demonstrate how tail composition plays a role in modulating the binding of PI(4,5)P2 lipids to GCGR Specifically, we find the PI(4,5)P2 lipids to have a higher affinity toward the inactive conformation Interestingly, we find that in contrast to class A GPCRs, PI(4,5)P2 appear to stabilize the inactive

To determine whether Gγ1 regulates uniquely rod phototransduction, we generated transgenic rods expressing Immunohistochemistry and Western blotting demonstrated the robust expression of each transgenic Gγ in rod cells and restoration of Gαt1 expression, which is greatly reduced in Gγ1-deficient rods. Thus, while farnesylated Gγ subunits are functionally active and largely interchangeable in supporting

We found that some agonist-induced GPCR/14-3-3 signal intensities can rapidly decrease. We confirmed that this phenomenon of rapidly decreasing agonist-induced GPCR/14-3-3 signal intensity Furthermore, we found that certain GPCR ligands can regulate GPCR/14-3-3 signals temporally, suggesting

Due to increasing numbers of people with excess body weight, the MC4R has become a target of interest We have previously reported that the MC4R forms homodimers, affecting receptor Gs signaling properties setmelanotide, a novel synthetic MC4R agonist, suggest a predominant role of the Gq/11 pathway regarding weight In this study, we analyzed effects of inhibiting homodimerization on Gq/11 signaling using previously MC4R (MC4R-WT).

In this work we present the study of the CX3CR1 receptor employing extensive atomistic Molecular Dynamics We analyzed the receptor conformational changes and described interactions within its key regions and Finally, we classify the features that would allow the identification of patterns that characterize a

GPR39 is a GPCR which can interact with Zn and modulate the colonocytes' survival. Materials: In our study, we compared GPR39 expression between colon cancers and tumor-adjacent tissues

However, it is unknown whether and how RAMP proteins may affect PTH1R function. Using different optical biosensors to measure the activation of PTH1R and its downstream signaling, we Employing homology modeling, we describe the putative structural molecular basis underlying our functional

September 2022 "G protein-coupled receptors (GPCRs) are signaling hubs in cell membranes that regulate a wide To explore the role of cholesterol in lateral dynamics of GPCRs, we utilized single particle tracking Notably, in cholesterol-depleted cells, we observed an increase in the confined population of the receptor These results are supported by our recent work and present observations that show polymerization of G-actin

natural killer cells from lymph nodes and playing a role in immune and neurodegenerative disorders, as well drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 The structure demonstrates a unique ligand-binding mode, involving an allosteric sub-pocket, which clarifies

Mutant heterodimers containing one wild-type (WT) and one mutant VFT domain, however, corresponding to Thus two WT VFT domains were required for normal Ca2+o potency and there was a pronounced gene-dosage In contrast, a single WT HH bundle was insufficient for maximal signaling and there was no functional difference between heterodimers in which the mutation was present in one or both intraloops; ie, no We consider how receptor asymmetry may support the underlying mechanisms. © 2022 The Authors.

Here we demonstrate that GPR84 is highly upregulated in inflamed colon tissues of active ulcerative colitis pro-inflammatory properties in colonic macrophages through enhancing NLRP3 inflammasome activation, while

All molecular components (bosentan, hETB, membrane, and solvent) were represented with an all-atom model Then sampling was conducted from conformations where bosentan was distant from the binding site in the

Somatostatin receptors (SSTs) are class A GPCRs abundantly expressed in pituitary tumors where they represent Moreover, whether octreotide or pasireotide may play modulatory effects and whether FLNA may participate First, we observed the formation of endogenous SST5 homo-dimers in GH3, A7, and M2 cells. Using the PLA approach combined with epitope tagging, we detected homo-dimers of human SST2 in GH3, A7 In conclusion, we demonstrated that in GH3 cells SST2 and SST5 can form both homo- and hetero-dimers

September 2022 "Background Cancer driver genes are usually ranked by mutation frequency, which does We hypothesize that driver strength is higher for genes preferentially mutated in patients with few driver Methods We propose formulas for the Driver Strength Index (DSI) and the Normalized Driver Strength We validate them using TCGA PanCanAtlas datasets, established driver prediction algorithms and custom

ADL5859 was docked to the inactive DOR and multiple microsecond molecular dynamic (MD) simulations were While the receptor with the crystal ligand (i.e. antagonist naltrindole) maintained the inactive conformation Major conformational differences were located on transmembrane (TM) 5 and 6, as well as intracellular The putative key residues (W274, D95, V267, L139, V263, M142, T260, R146, R258 and others) involving distance analysis, which provides a short list for experimental mutagenesis study.

transmembrane domain, Class F GPCR family protein) plays a crucial role in the Hedgehog (HH) signaling pathway, which HH binding leads to the dislocation of PTC1 from the cilia, thus making way for SMO to localize in the We have carried out MARTINI coarse-grained molecular dynamics simulations of SMO in POPC and in ciliary We are able to identify the interaction of membrane cholesterols with definite sites and domains within may well steer cholesterol into the hitherto identified binding sites within the TMD of SMO.

September 2022 "RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which

This article focussed on emerging fields based on the authors’ current work and expertise. Regulatory autoantibodies (abs) are discussed, which are parts of the human physiology and are specifically Promising nuclear receptors as key regulators of transcriptional programmes will be introduced as well as epigenetic modifications, which are pivotal to maintain the profibrotic fibroblast phenotype independent , which promote fibroblast-to-myofibroblast transition and extracellular matrix generation.

G-protein–coupled receptor pathway is inhibited by the regulator of G-protein signaling (RGS) Sst2 which G-protein signaling activates the MAPK Fus3, which phosphorylates the RGS; however, the role of this We found that pheromone-induced RGS phosphorylation peaks early; the phospho-state of RGS controls its We found that RGS complexes with Kel1 and prefers the unphosphorylatable RGS mutant. We also found overexpression of unphosphorylatable RGS exacerbates cytokinetic defects, whereas they

It is generally considered that TNBC is an estrogen-independent breast cancer, while a new estrogen receptor Besides, high GPER expression was significantly linked to the worse survival in patients with lymph node metastasis, TNM stage III as well as nuclear grade G3 tumors.

Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular

September 2022 "The function of the actin cytoskeleton in cellular motility and trafficking has been widely In a recent work, we reported that chronic cholesterol depletion using statins leads to significant polymerization In this work, we explore the effect of reorganization of the actin cytoskeleton on membrane dynamics Specifically, we explore the role of actin cytoskeleton in regulating the dynamics of the serotonin1A For this, we analyzed the lateral dynamics of the serotonin1A receptor in cholesterol-depleted cells

Structurally, the extensive extracellular domain, which contains the hormone-binding site and is linked We combined in vitro and in situ chemical crosslinking, disulfide pattern analysis, and mutation data