Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Arginylation Regulates G-protein Signaling in the Retina.

ABSTRACT: Arginylation is a post-translational modification mediated by the arginyltransferase (Ate1). We recently showed that conditional deletion of Ate1 in the nervous system leads to increased light-evoked response sensitivities of ON-bipolar cells in the retina, indicating that arginylation regulates the G-protein signaling complexes of those neurons and/or photoreceptors. However, none of the key players in the signaling pathway were previously shown to be arginylated. Here we show that Gαt1, Gβ1, RGS6, and RGS7 are arginylated in the retina and RGS6 and RGS7 protein levels are elevated in Ate1 knockout, suggesting that arginylation plays a direct role in regulating their protein level and the G-protein-mediated responses in the retina.

SUBMITTER: Fina ME

PROVIDER: S-EPMC8815403 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Arginylation Regulates G-protein Signaling in the Retina.

Fina Marie E ME Wang Junling J Vedula Pavan P Tang Hsin-Yao HY Kashina Anna A Dong Dawei W DW

Frontiers in cell and developmental biology 20220121

Arginylation is a post-translational modification mediated by the arginyltransferase (Ate1). We recently showed that conditional deletion of Ate1 in the nervous system leads to increased light-evoked response sensitivities of ON-bipolar cells in the retina, indicating that arginylation regulates the G-protein signaling complexes of those neurons and/or photoreceptors. However, none of the key players in the signaling pathway were previously shown to be arginylated. Here we show that G<i>α</i>t1, ...[more]

PMID: 35127722

Similar Datasets

Protein arginylation regulates cellular stress response by stabilizing HSP70 and HSP40 transcripts.

Project description:ATE1-mediated post-translational addition of arginine to a protein has been shown to regulate activity, interaction, and stability of the protein substrates. Arginylation has been linked to many different stress conditions, namely ER stress, cytosolic misfolded protein stress, and nitrosative stress. However, clear understanding about the effect of arginylation in cellular stress responses is yet to emerge. In this study, we investigated the role of arginylation in heat-stress response. Our findings suggest that Ate1 knock out (KO) cells are more susceptible to heat stress compared with its wild-type counterparts due to the induction of apoptosis in KO cells. Gene expression analysis of inducible heat-shock proteins (HSP70.1, HSP70.3, and HSP40) showed induction of these genes in KO cells early in the heat shock, but were drastically diminished at the later period of heat shock. Further analysis revealed that loss of ATE1 drastically reduced the stability of all three HSP mRNAs. These phenotypes were greatly restored by overexpression of Ate1 in KO cells. Our findings show that arginylation plays a protective role during heat stress by regulating HSP gene expression and mRNA stability.

| S-EPMC5045964 | biostudies-literature

Notch signaling regulates regeneration in the avian retina.

Project description:The chicken retina is capable of limited regeneration. In response to injury, some Müller glia proliferate and de-differentiate into progenitor cells. However, most of these progenitors fail to differentiate into neurons. The Notch pathway is upregulated during retinal regeneration in both fish and amphibians. Since the Notch signaling pathway maintains cells in a progenitor state during development, we hypothesized that a persistently active Notch pathway might prevent a more successful regeneration in the chick retina. We found that Notch signaling components are upregulated in the proliferating progenitors. We also found that blocking the Notch pathway while Müller glia are de-differentiating into progenitor cells prohibits regeneration; conversely, blocking the Notch pathway after the progenitors have been generated from the Müller glia caused a significant increase in the percentage of new neurons. Thus, Notch signaling appears to play two distinct roles during retinal regeneration. Initially, Notch activity is necessary for the de-differentiation/proliferation of Müller glia, while later it inhibits the differentiation of the newly generated progenitor cells.

| S-EPMC2170876 | biostudies-literature

tRNAArg-derived fragments mediate protein arginylation

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-08-12 | GSE146344 | GEO

Global analysis of posttranslational protein arginylation.

Project description:Posttranslational arginylation is critical for embryogenesis, cardiovascular development, and angiogenesis, but its molecular effects and the identity of proteins arginylated in vivo are largely unknown. Here we report a global analysis of this modification on the protein level and identification of 43 proteins arginylated in vivo on highly specific sites. Our data demonstrate that unlike previously believed, arginylation can occur on any N-terminally exposed residue likely defined by a structural recognition motif on the protein surface, and that it preferentially affects a number of physiological systems, including cytoskeleton and primary metabolic pathways. The results of our study suggest that protein arginylation is a general mechanism for regulation of protein structure and function and outline the potential role of protein arginylation in cell metabolism and embryonic development.

| S-EPMC1988855 | biostudies-literature

Arginylation of myosin heavy chain regulates skeletal muscle strength.

Project description:Protein arginylation is a posttranslational modification with an emerging global role in the regulation of actin cytoskeleton. To test the role of arginylation in the skeletal muscle, we generated a mouse model with Ate1 deletion driven by the skeletal muscle-specific creatine kinase (Ckmm) promoter. Ckmm-Ate1 mice were viable and outwardly normal; however, their skeletal muscle strength was significantly reduced in comparison to controls. Mass spectrometry of isolated skeletal myofibrils showed a limited set of proteins, including myosin heavy chain, arginylated on specific sites. Atomic force microscopy measurements of contractile strength in individual myofibrils and isolated myosin filaments from these mice showed a significant reduction of contractile forces, which, in the case of myosin filaments, could be fully rescued by rearginylation with purified Ate1. Our results demonstrate that arginylation regulates force production in muscle and exerts a direct effect on muscle strength through arginylation of myosin.

| S-EPMC4126752 | biostudies-literature

tRNAArg-derived fragments mediate protein arginylation [tRNA]

Project description:Arginyltransferase ATE1 mediates posttranslational arginylation that plays key roles in mammalian embryogenesis, cell migration, and normal brain function. The molecular mechanisms of arginylation remain elusive. ATE1 utilizes arginyl-tRNAArg as the donor of Arg, putting this reaction into a direct competition with the protein synthesis machinery. Here, we addressed these questions of ATE1- arginyl-tRNAArg specificity as a potential mechanism enabling this competition in vivo. Using in vitro arginylation assays and ATE1 knockout models, we find that while arginylation is specific to tRNAArg, it is able to utilize short tRNAArg derivatives that bear structural resemblance to tRNA-derived fragments (tRF), a new class of small regulatory non-coding RNAs with poorly characterized but critical functions in vivo. Arginyl-tRFArg can be generated in vitro directly from pre-charged -tRNAArg, and ATE1 is able to utilize these arginyl-tRFArg fragments with similar efficiency as arginyl-tRNAArg. Lack of arginylation in ATE1 knockout cells leads to a decrease in tRFArg generation and a significant increase in the ratio of tRNAArg to tRFArg compared to wild type, suggesting a functional link between tRFArg and arginylation in vivo. We propose that generation of physiologically important tRFs can play a critical role as a switch between protein translation and arginylation in vivo.

2020-08-12 | GSE146343 | GEO

tRNAArg-derived fragments mediate protein arginylation [tRF]

2020-08-12 | GSE146342 | GEO

Canonical wingless signaling regulates cone cell specification in the Drosophila retina.

Project description:Correct tissue patterning during development involves multiple morphogenetic events that include specification of different cell fates, cell proliferation, cell death, and coordinated changes in cell shape, position, and adhesion. Here, we use the Drosophila retina to explore the molecular mechanisms that regulate and integrate these various events. In a previous report, we found that wingless (wg) was required to induce a previously unknown surge of cell death ("early death") in the pupal retina. Here, we show that wg is also required to induce the more widely studied mid-pupal cell death ("late death") in a process that involves regulation of DIAP1. Furthermore, our data suggest that wg has a previously unreported role in specifying the glial-like cone cells. This activity requires canonical Wg signaling and is linked with Notch pathway activity. Our work broadens the role of canonical Wg signaling to encompass multiple patterning steps in the emerging Drosophila retina.

| S-EPMC2892184 | biostudies-literature

Arginylation regulates myofibrils to maintain heart function and prevent dilated cardiomyopathy.

Project description:Protein arginylation mediated by arginyltransferase (ATE1) is essential for heart formation during embryogenesis, however its cell-autonomous role in cardiomyocytes and the differentiated heart muscle has never been investigated. To address this question, we generated cardiac muscle-specific Ate1 knockout mice, in which Ate1 deletion was driven by α-myosin heavy chain promoter (αMHC-Ate1 mouse). These mice were initially viable, but developed severe cardiac contractility defects, dilated cardiomyopathy, and thrombosis over time, resulting in high rates of lethality after 6months of age. These symptoms were accompanied by severe ultrastructural defects in cardiac myofibrils, seen in the newborns and far preceding the onset of cardiomyopathy, suggesting that these defects were primary and likely underlay the development of the future heart defects. Several major sarcomeric proteins were arginylated in vivo. Moreover, Ate1 deletion in the hearts resulted in a significant reduction of active and passive myofibril forces, suggesting that arginylation is critical for both myofibril structural integrity and contractility. Thus, arginylation is essential for maintaining the heart function by regulation of the major myofibril proteins and myofibril forces, and its absence in the heart muscle leads to progressive heart failure through cardiomyocyte-specific defects.

| S-EPMC3418387 | biostudies-literature

Dynamic decapentaplegic signaling regulates patterning and adhesion in the Drosophila pupal retina.

Project description:The correct organization of cells within an epithelium is essential for proper tissue and organ morphogenesis. The role of Decapentaplegic/Bone morphogenetic protein (Dpp/BMP) signaling in cellular morphogenesis during epithelial development is poorly understood. In this paper, we used the developing Drosophila pupal retina--looking specifically at the reorganization of glial-like support cells that lie between the retinal ommatidia--to better understand the role of Dpp signaling during epithelial patterning. Our results indicate that Dpp pathway activity is tightly regulated across time in the pupal retina and that epithelial cells in this tissue require Dpp signaling to achieve their correct shape and position within the ommatidial hexagon. These results point to the Dpp pathway as a third component and functional link between two adhesion systems, Hibris-Roughest and DE-cadherin. A balanced interplay between these three systems is essential for epithelial patterning during morphogenesis of the pupal retina. Importantly, we identify a similar functional connection between Dpp activity and DE-cadherin and Rho1 during cell fate determination in the wing, suggesting a broader link between Dpp function and junctional integrity during epithelial development.

| S-EPMC2957290 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data