Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Role of the Visual Conditioning-Dependent Nascent Proteome in Neuronal Plasticity

ABSTRACT: Experience-dependent synaptic plasticity refines brain circuits during development. To uncover protein synthesis-dependent mechanisms contributing to experience-dependent plasticity, we performed quantitative proteomic analysis of the nascent proteome using improved bio-orthogonal metabolic labeling (BONCAT) to identify candidate plasticity proteins (CPPs) that undergo differential protein synthesis in response to visual conditioning (VC) in Xenopus optic tectum. We identified 83 CPPs that formed strongly connected networks and were annotated to a variety of biological functions, including RNA splicing, protein translation, and chromatin remodeling. Functional analysis of select CPPs using translation blocking morpholinos revealed the requirement of eukaryotic initiation factor 3 subunit A (eIF3A), fused in sarcoma (FUS), and ribosomal protein s17 (RPS17) in experience-dependent structural plasticity of tectal neurons. These results demonstrate that the nascent proteome is dynamic in response to VC and that de novo synthesis of the machinery that regulates gene expression and protein translation is required for experience-dependent structural plasticity.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Xenopus Laevis/gilli (ncbitaxon:8359)

SUBMITTER: Hollis T. Cline

PROVIDER: MSV000081728 | MassIVE | Tue Nov 21 08:54:00 GMT 2017

SECONDARY ACCESSION(S): PXD008694

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Similar Datasets

Acute synthesis of CPEB is required for plasticity of visual avoidance behavior in Xenopus

Project description:Neural plasticity requires protein synthesis, but the identity of newly synthesized proteins generated in response to plasticity-inducing stimuli remains unclear. We used in vivo bio-orthogonal noncanonical amino acid tagging (BONCAT) with the methionine analog azidohomoalanine (AHA) combined with the multidimensional protein identification technique (MudPIT) to identify proteins that are synthesized in the tadpole brain over 24 hr. We induced conditioning-dependent plasticity of visual avoidance behavior, which required N-methyl-D-aspartate (NMDA) and Ca(2+)-permeable alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, alphaCaMKII, and rapid protein synthesis. Combining BONCAT with western blots revealed that proteins including alphaCaMKII, MEK1, CPEB, and GAD65 are synthesized during conditioning. Acute synthesis of CPEB during conditioning is required for behavioral plasticity as well as conditioning-induced synaptic and structural plasticity in the tectal circuit. We outline a signaling pathway that regulates protein-synthesis-dependent behavioral plasticity in intact animals, identify newly synthesized proteins induced by visual experience, and demonstrate a requirement for acute synthesis of CPEB in plasticity.

2018-01-11 | MSV000081914 | MassIVE

The Integrated Stress Response effector GADD34 is repurposed by neurons to promote stimulus-induced translation

Project description:Neuronal protein synthesis is required for long-lasting plasticity and long-term memory consolidation. Dephosphorylation of eukaryotic initiation factor 2α is one of the key translational control events that is required to increase de novo protein synthesis that underlies long-lasting plasticity and memory consolidation. Here, we interrogate the molecular pathways of translational control that are triggered by neuronal stimulation with brain-derived neurotrophic factor (BDNF), which results in eIF2α dephosphorylation and de novo protein synthesis. Primary rodent neurons exposed to BDNF displayed elevated translation, but not transcription, of GADD34, which facilitates eIF2α dephosphorylation and subsequent de novo protein synthesis. Furthermore, GADD34 requires G-actin generated by cofilin to dephosphorylate eIF2α and enhance protein synthesis. Finally, GADD34 is required for BDNF-induced translation of synaptic plasticity-related proteins. Overall, we provide evidence that neurons repurpose GADD34, an effector of the Integrated Stress Response, as an orchestrator of rapid increases in eIF2-dependent translation in response to plasticity-inducing stimuli.

2023-11-22 | GSE248013 | GEO

Genes with 5′ terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 NSP1 protein

Project description:Viruses rely on the host translation machinery to synthesize their own proteins. Consequently, they have evolved varied mechanisms to co-opt host translation for their survival. SARS-CoV-2 relies on a non-structural protein, NSP1, for shutting down host translation. Despite this, it is currently unknown how viral proteins and host factors critical for viral replication can escape a global shutdown of host translation. Here, using a novel FACS-based assay called MeTAFlow, we report a dose-dependent reduction in both nascent protein synthesis and mRNA abundance in cells expressing NSP1. We perform RNA-Seq and matched ribosome profiling experiments to identify gene-specific changes both at the mRNA expression and translation level. We discover a functionally-coherent subset of human genes preferentially translated in the context of NSP1 expression. These genes include the translation machinery components, RNA binding proteins, and others important for viral pathogenicity. Importantly, we also uncover potential mechanisms of preferential translation through the presence of shared sites for specific RNA binding proteins and a remarkable enrichment for 5′ terminal oligo-pyrimidine tracts. Collectively, the present study suggests fine tuning of host gene expression and translation by NSP1 despite its global repressive effect on host protein synthesis.

2020-10-01 | GSE158374 | GEO

Mutant FUS triggers age-dependent synaptic impairment in presymptomatic ALS-FUS mice (RNA-seq part2)

Project description:FUS is a primarily nuclear RNA-binding protein with important roles in RNA processing and transport. FUS mutations disrupting its nuclear localization characterize a subset of amyotrophic lateral sclerosis (ALS-FUS) patients, through an unidentified pathological mechanism. FUS regulates nuclear RNA, but its role at the synapse is poorly understood. Here, we used super-resolution imaging to determine the physiological localization of extranuclear, neuronal FUS and found it predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosome preparations, we identified synaptic RNA targets of FUS that are associated with synapse organization and plasticity. Synaptic FUS was significantly increased in a knock-in mouse model of ALS-FUS, at presymptomatic stages. Despite apparently unaltered synaptic organization, RNA-seq of synaptoneurosomes highlighted age-dependent dysregulation of glutamatergic and GABAergic synapses. Our study indicates that FUS relocalization to the synapse in early stages of ALS-FUS results in synaptic impairment, potentially representing an initial trigger of neurodegeneration.

2021-03-05 | E-MTAB-10104 | biostudies-arrayexpress

Mutant FUS triggers age-dependent synaptic impairment in presymptomatic ALS-FUS mice (CLIP-seq)

2021-03-05 | E-MTAB-9211 | biostudies-arrayexpress

Mutant FUS triggers age-dependent synaptic impairment in presymptomatic ALS-FUS mice (RNA-seq)

2021-03-05 | E-MTAB-9212 | biostudies-arrayexpress

CB1 receptor-mediated inhibitory LTD triggers presynaptic remodeling via protein synthesis and ubiquitination

Project description:Long-lasting forms of postsynaptic plasticity commonly involve protein synthesis-dependent structural changes of dendritic spines. However, the relationship between protein synthesis and presynaptic structural plasticity remains unclear. Here, we investigated structural changes in cannabinoid-receptor 1 (CB1)-mediated long-term depression of inhibitory transmission (iLTD), a form of presynaptic plasticity that requires protein synthesis and involves a long-lasting reduction in GABA release. We found that CB1-iLTD in acute rat hippocampal slices was associated with protein synthesis-dependent presynaptic structural changes. Using proteomics, we determined that CB1 activation in hippocampal neurons resulted in increased ribosomal proteins and initiation factors, but decreased levels of proteins involved in regulation of the actin cytoskeleton, such as Arp2/3, and presynaptic release. Moreover, while CB1-iLTD increased ubiquitin/proteasome activity, ubiquitination but not proteasomal degradation was critical for structural and functional presynaptic CB1-iLTD. Thus, CB1-iLTD relies on both protein synthesis and ubiquitination to elicit structural changes that underlie long-term reduction of GABA release.

2020-09-23 | PXD020008 | Pride

RNA-Seq in hippocampus of control and Jade2-KO mice

Project description:Impairment of synaptic plasticity is involved in a range of pathological conditions such as cognitive deficits. However, how synaptic efficacy is regulated is not fully understood. Here, we report that the epigenetic factor Jade family PHD finger 2 (JADE2), which is upregulated by neuronal activities, is critically involved in the maintenance of hippocampal synaptic plasticity and cognitive functions in mice. Knockdown or genetic deletion of JADE2 in hippocampal CA1 results in impaired structural and functional synaptic plasticity, leading to memory impairment, whereas overexpression of JADE2 in CA1 neurons facilitates hippocampal-dependent learning and memory. Mechanistically, we show that JADE2 modulates synaptic functions mainly by transcriptional activation of cytoskeletal protein RAC1, and this activity is dependent on its interaction with histone acetyltransferase HBO1. Together, our findings suggest JADE2 is a critical player for experience-dependent gene regulation in controlling synaptic plasticity and cognitive functions.

2022-04-11 | GSE197460 | GEO

4E-BP1-dependent translation in microglia controls mechanical hypersensitivity

Project description:Spinal microglia play a pivotal role in the development of neuropathic pain. Peripheral nerve injury induces changes in the transcriptional profile of microglia, including increased expression of components of translational machinery. Whether microglial protein synthesis is stimulated following nerve injury and has a functional role in mediating pain hypersensitivity is unknown. Here, we show that nascent protein synthesis is upregulated in spinal microglia following peripheral nerve injury. Stimulating mRNA translation in microglia, via selective ablation of the translational repressor, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), promoted the transition of microglia to a reactive state and induced mechanical hypersensitivity. Conversely, inhibiting microglial translation by expressing mutant 4E-BP1 in microglia attenuated their peripheral nerve injury-induced activation and alleviated neuropathic pain. Thus, the stimulation of 4E-BP1-dependent translation promotes microglia reactivity and mechanical hypersensitivity, whereas its inhibition alleviates neuropathic pain.

2024-01-31 | GSE254472 | GEO

IFNγ protects motor neurons from oxidative stress via enhanced global protein synthesis in FUS-associated Amyotrophic Lateral Sclerosis

Project description:Amyotrophic lateral sclerosis type 6 (ALS6) is a familial subtype of ALS linked to Fused in Sarcoma (FUS) gene mutation. FUS mutations lead to decreased global protein synthesis, but the mechanism that drives this has not been established. Here, we used ALS6 patient-derived induced pluripotent stem cells (hIPSCs) to study the effect of the ALS6 FUSR521H mutation on the translation machinery in motor neurons (MNs). We find, in agreement with findings of others, that protein synthesis is decreased in ALS6 MNs. Furthermore, ALS6 MNs are more sensitive to oxidative stress and display reduced expression of TGF-β and mTORC gene pathways when stressed. Finally, we show that IFNγ treatment reduces apoptosis of ALS6 MNs exposed to oxidative stress and partially restores the translation rates in ALS6 MNs. Overall, these findings suggest that a functional IFNγ response is important for FUS-mediated protein synthesis, possibly by FUS nuclear translocation in ALS6.

2024-01-26 | PXD038042 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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