scholarly journals Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis

2018 ◽  
Author(s):  
Axel Schmidt ◽  
Philipp Bauknecht ◽  
Elizabeth A. Williams ◽  
Katrin Augustinowski ◽  
Stefan Gründer ◽  
...  
Keyword(s):  
Target Cells ◽  
Metabotropic Receptors ◽  
Platynereis Dumerilii ◽  
Gated Channel ◽  
Additional Level ◽  
Cell Transcriptome ◽  
Transcriptome Resource ◽  
Single Cell Transcriptome ◽  
G Protein Coupled ◽  
Ionotropic And Metabotropic Receptors

AbstractNeuropeptides commonly signal by metabotropic G-protein coupled receptors (GPCRs). In some mollusks and cnidarians, RFamide neuropeptides mediate fast ionotropic signaling by peptide-gated ion channels that belong to the DEG/ENaC family. Here we describe a neuropeptide system with a dual mode of signaling by both a peptide-gated channel and a GPCR. We identified and characterised a peptide-gated channel in the marine annelid Platynereis dumerilii that is specifically activated by Wamide myoinhibitory peptides derived from the same proneuropeptide. The myoinhibitory peptide-gated ion channel (MGIC) belongs to the DEG/ENaC family and is paralogous to RFamide-gated channels. Platynereis myoinhibitory peptides also activate a previously described GPCR, MAG. We measured the potency of all Wamides on both MGIC and MAG and identified peptides that preferentially activate one or the other receptor. Analysis of a single-cell transcriptome resource indicates that MGIC and MAG signal to distinct target neurons. The identification of a Wamide-gated channel suggests that peptide-gated channels are more diverse and widespread in animals than previously appreciated. The possibility of neuropeptide signaling by both ionotropic and metabotropic receptors to different target cells in the same organism highlights an additional level of complexity in peptidergic signaling networks.

Protective action of the microbial metabolite butyrate against cardiomyocyte hypertrophy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Umei ◽  
H Akazawa ◽  
A Saga-Kamo ◽  
H Yagi ◽  
Q Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Short Chain Fatty Acid ◽  
Short Chain Fatty Acids ◽  
Chain Fatty Acid ◽  
G Protein Coupled Receptors ◽  
Short Chain ◽  
Cardiomyocyte Hypertrophy ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
G Protein Coupled

Abstract Introduction Short-chain fatty acids are one of the gut microbial metabolites that may influence host physiology. We previously reported that gut dysbiosis was associated with heart failure, and that the proportions of butyrate-producing bacteria diminished prominently in the gut of patients with heart failure. Purpose We investigated the molecular mechanism of butyrate and investigated the protective mechanism against heart failure. Methods We searched for G protein-coupled receptors for short-chain fatty acids using single-cell transcriptome analysis of cardiomyocytes and non-cardiomyocytes isolated from murine hearts. In addition, we examined the effects of butyrate on endothelin-1 (ET1) or isoproterenol-induced hypertrophic responses and histone deacetylase (HDAC) activities in cultured neonatal rat cardiomyocytes. Results Single-cell transcriptome analysis and co-expression network analysis revealed that G protein-coupled receptors for short-chain fatty acid receptors were not expressed in cardiomyocytes and that Olfr78 was expressed in vascular smooth muscle cells in the heart. Treatment with butyrate inhibited ET1-induced hypertrophic growth and up-regulation of the genes such as Nppa, Acta1, and Myh7 in cultured rat neonatal cardiomyocytes. Moreover, butyrate increased the acetylation levels of histone H3, indicating that butyrate has an inhibitory effect on HDAC in cardiomyocytes. In addition, treatment with butyrate caused up-regulation of Inpp5f, encoding inositol polyphosphate-5-phosphatase f, which was associated with a significant decrease in the phosphorylation levels of Akt. These results suggest that butyrate may act as HDAC inhibitor to increase Inpp5f gene expression, leading to the activation of Akt-glycogen synthase kinase 3beta (Gsk3beta) pathway, and thereby protect against hypertrophic responses. Conclusion There was no known GPCR for short-chain fatty acid expressed in cardiomyocytes. However, butyrate suppressed cardiomyocyte hypertrophy through epigenetic modification of gene expression. Our results may uncover a potential role of the dysbiosis of intestinal microbiota in the pathogenesis of cardiac hypertrophy and failure. Funding Acknowledgement Type of funding source: None

Receiving the Synaptic Message

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Adrenergic Receptors ◽  
Acetylcholine Receptors ◽  
G Protein Coupled Receptors ◽  
Metabotropic Receptors ◽  
Second Messenger Systems ◽  
Psychotropic Effects ◽  
G Protein Coupled ◽  
Ionotropic And Metabotropic Receptors

Ionotropic and metabotropic receptors differ in their speed of action, the variety of effects produced after ligand-binding, and in the number of types present in the nervous system. The participation of two ionotropic glutamate receptors in synaptic plasticity is thought to be the cellular basis of learning. The actions of acetylcholine on nicotinic acetylcholine receptors present at the neuromuscular junction are described. The pharmacological profile of the GABAA receptor, central to most neural functions, is introduced. The properties of metabotropic receptors that are coupled to G proteins, termed G protein-coupled receptors (GPCRs), are detailed. Three canonical second-messenger systems through which GPCRs act are briefly described. An introduction to clinical pharmacology focused on how drugs acting on muscarinic and adrenergic receptors produce peripheral and central psychotropic effects is provided. Finally, the role of connexins and gap junctions in myelination and hearing is introduced.

scholarly journals Single-Cell Transcriptome Sequencing and Proteomics Reveal Neonatal Ileum Dynamic Developmental Potentials

mSystems ◽  
2021 ◽  
Author(s):  
Qingshi Meng ◽  
Liang Chen ◽  
Bohui Xiong ◽  
Beining Kang ◽  
Pengfei Zhang ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Secretory Cells ◽  
Protein Signaling ◽  
Morphogenetic Protein ◽  
Undifferentiated Cells ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
G Protein Coupled ◽  
Enterocyte Differentiation

We found previously unknown neonatal ileum developmental potentials: specific increases in undifferentiated cells, unique enterocyte differentiation, and time dependent reduction in secretory cells. Specific transcriptional factors (TFs), ligand-receptor pairs, G protein-coupled receptors, transforming growth factor β, bone morphogenetic protein signaling pathways, and the gut mucosal microbiota are involved in this process.

scholarly journals Synaptic and peptidergic connectome of a neurosecretory center in the annelid brain

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Elizabeth A Williams ◽  
Csaba Verasztó ◽  
Sanja Jasek ◽  
Markus Conzelmann ◽  
Réza Shahidi ◽  
...  
Keyword(s):  
Cell Types ◽  
Peptide Receptor ◽  
Behavior Understanding ◽  
Transmission Electron ◽  
Neurosecretory Neurons ◽  
Platynereis Dumerilii ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
And Behavior ◽  
The Brain

Neurosecretory centers in animal brains use peptidergic signaling to influence physiology and behavior. Understanding neurosecretory center function requires mapping cell types, synapses, and peptidergic networks. Here we use transmission electron microscopy and gene expression mapping to analyze the synaptic and peptidergic connectome of an entire neurosecretory center. We reconstructed 78 neurosecretory neurons and mapped their synaptic connectivity in the brain of larval Platynereis dumerilii, a marine annelid. These neurons form an anterior neurosecretory center expressing many neuropeptides, including hypothalamic peptide orthologs and their receptors. Analysis of peptide-receptor pairs in spatially mapped single-cell transcriptome data revealed sparsely connected networks linking specific neuronal subsets. We experimentally analyzed one peptide-receptor pair and found that a neuropeptide can couple neurosecretory and synaptic brain signaling. Our study uncovered extensive networks of peptidergic signaling within a neurosecretory center and its connection to the synaptic brain.

scholarly journals Transcriptional profiling of mouse peripheral nerves to the single-cell level to build a sciatic nerve ATlas (SNAT)

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Daniel Gerber ◽  
Jorge A Pereira ◽  
Joanne Gerber ◽  
Ge Tan ◽  
Slavica Dimitrieva ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Single Cell ◽  
Rna Sequencing ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Cell Transcriptome ◽  
Transcriptome Resource ◽  
Single Cell Transcriptome

Peripheral nerves are organ-like structures containing diverse cell types to optimize function. This interactive assembly includes mostly axon-associated Schwann cells, but also endothelial cells of supporting blood vessels, immune system-associated cells, barrier-forming cells of the perineurium surrounding and protecting nerve fascicles, and connective tissue-resident cells within the intra-fascicular endoneurium and inter-fascicular epineurium. We have established transcriptional profiles of mouse sciatic nerve-inhabitant cells to foster the fundamental understanding of peripheral nerves. To achieve this goal, we have combined bulk RNA sequencing of developing sciatic nerves up to the adult with focused bulk and single-cell RNA sequencing of Schwann cells throughout postnatal development, extended by single-cell transcriptome analysis of the full sciatic nerve both perinatally and in the adult. The results were merged in the transcriptome resource Sciatic Nerve ATlas (SNAT:https://www.snat.ethz.ch). We anticipate that insights gained from our multi-layered analysis will serve as valuable interactive reference point to guide future studies.

scholarly journals Single cell transcriptome atlas of mouse mammary epithelial cells across development

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Bhupinder Pal ◽  
Yunshun Chen ◽  
Michael J. G. Milevskiy ◽  
François Vaillant ◽  
Lexie Prokopuk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cell ◽  
Developmental Stages ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Single Cells ◽  
Chromatin Accessibility ◽  
Mammary Epithelial ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during mammary ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, and post-involution, as well as the transcriptomes of micro-dissected terminal end buds (TEBs) and subtending ducts during puberty. Methods The single cell transcriptomes of 132,599 mammary epithelial cells from 9 different developmental stages were determined on the 10x Genomics Chromium platform, and integrative analyses were performed to compare specific time points. Results The mammary rudiment at E18.5 closely aligned with the basal lineage, while prepubertal epithelial cells exhibited lineage segregation but to a less differentiated state than their adult counterparts. Comparison of micro-dissected TEBs versus ducts showed that luminal cells within TEBs harbored intermediate expression profiles. Ductal basal cells exhibited increased chromatin accessibility of luminal genes compared to their TEB counterparts suggesting that lineage-specific chromatin is established within the subtending ducts during puberty. An integrative analysis of five stages spanning the pregnancy cycle revealed distinct stage-specific profiles and the presence of cycling basal, mixed-lineage, and 'late' alveolar intermediates in pregnancy. Moreover, a number of intermediates were uncovered along the basal-luminal progenitor cell axis, suggesting a continuum of alveolar-restricted progenitor states. Conclusions This extended single cell transcriptome atlas of mouse mammary epithelial cells provides the most complete coverage for mammary epithelial cells during morphogenesis to date. Together with chromatin accessibility analysis of TEB structures, it represents a valuable framework for understanding developmental decisions within the mouse mammary gland.

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