Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA386335 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5529000_1.fastq.gz | Fastqsanger.gz | |||
| SRR5529000_2.fastq.gz | Fastqsanger.gz | |||
| SRR5529010_1.fastq.gz | Fastqsanger.gz | |||
| SRR5529010_2.fastq.gz | Fastqsanger.gz | |||
| SRR5529001_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
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Project description:CLN1 disease (OMIM #256730) is an early childhood ceroid-lipofuscinosis associated with mutated CLN1, whose product (PPT1) is a lysosomal enzyme involved in the removal of palmitate residues from S-acylated proteins. In neurons, PPT1 is also related to specific functions in the synaptic compartment. The aim of this study was to recognize molecular signatures and functional modules connected with CLN1. We utilized differentiated SH-SY5Y neuroblastoma cells to overexpress wild type CLN1 (SH-p.wtCLN1) and introduced selected mutations previously detected in CLN1 patients. wtCLN1 and two mutant CLN1- harbouring cell lines were characterized by whole transcriptomic profiling using RNA-seq, to subsequently identify differentially expressed genes (DEGs) and alterations in related neuronal functions.
2017-09-20 | GSE98834 | GEO
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. 4 samples analysed, 3 coverslips pooled per sample. Mouse DRG neuron cell bodies and axons were separated in multicompartment cell cultures allowing electrical stimulation of axons, growing under a high-resistance partition between compartments, through platinum electrodes in the lid of the culture dish (Reference: http://www.ncbi.nlm.nih.gov/pubmed/9295372)
2014-03-12 | E-GEOD-55779 | biostudies-arrayexpress
Project description:We report here the identification of substrates of the depalmitoylating enzyme PPT1 by quantitative mass spectrometry. We utilized a stringent two-step Acyl Resin-Assisted Capture (Acyl RAC) screen in which increased palmitoylation in vivo in PPT1 knockout is the first selection criteria for substrates. We validated hits by direct depalmitoylation with PPT1 to identify bona fide substrates. Most proteins identified are previously reported to be palmitoylated and the few known PPT1 substrates were validated. Significantly, the screen identified >100 proteins not previously known to be depalmitoylated by PPT1, including a wide range of endocytic, signaling, synaptic adhesion, mitochondrial, and lysosomal proteins. These proteins collectively explain the many facets of CLN1 disease caused by the loss of PPT1 function. We determined that an Ig domain in synaptic adhesion molecules may be a PPT1 recognition site for depalmitoylation. Finally, we provide evidence that PPT1 participates in neuronal activity-dependent palmitoylation-depalmitoylation cycles at the synapse.
2022-05-19 | PXD017270 | Pride
Project description:Local translation within excitatory and inhibitory neurons is known to be involved in neuronal development and synaptic plasticity. Despite the extensive dendritic and axonal arborizations of monoaminergic neurons, the subcellular localization of protein synthesis has not been well-characterized in these populations. Here, we investigated mRNA localization in midbrain dopaminergic (mDA) neurons, cells with enormous axonal and dendritic projections, both of which can release dopamine (DA). Using highly-sensitive sequencing and imaging approaches in mDA axons, we found no evidence for axonal mRNA localization or translation. In contrast, we found that mDA neuronal dendritic projections into the substantia nigra reticulata (SNr) contain ribosomes and mRNAs encoding the DA synthesis, release, and reuptake machinery. Surprisingly, we found dendritic localization of mRNAs encoding synaptic vesicular release proteins in mDA neurons. Our results are consistent with a role for local translation in the regulation of DA transmission from dendrites, but not striatal axons. Finally, we defined a molecular signature of sparse mDA neurons in the SNr, including enrichment of an ER calcium pump previously undescribed in mDA neurons.
2021-07-27 | GSE180913 | GEO
Project description:The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses to neuronal stimulation are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt. In particular, changes in the phosphoproteome in the cell body are involved in the reorganisation of the cytoskeleton and in axonal terminals the regulation of synaptic and secretory processes. We have identified that prohormone precursors including vasopressin and oxytocin are phosphorylated in axonal terminals and are hyperphosphorylated following stimulation. By multi-omic integration of transcriptome and proteomic data we identify changes to proteins present in afferent inputs to this nucleus.
2023-04-12 | PXD040870 | Pride
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. 12 hippocampal cell culture samples analysed, 3 coverslips pooled per sample. Treatments are as follows: Block: an inhibitor cocktail containing 50 µM D-APV, 40 µM CNQX, and 100 nM TTX for 3 hrs Activity: 50 µM bicuculline (BiC)/500 µM 4-Aminopyridine ActD: 25 µM actinomycin D
2014-03-12 | E-GEOD-55777 | biostudies-arrayexpress
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. 12 hippocampal cell culture samples analysed, 3 coverslips pooled per sample. Treatments are as follows: Block: an inhibitor cocktail containing 50 µM D-APV, 40 µM CNQX, and 100 nM TTX for 3 hrs Activity: 50 µM bicuculline (BiC)/500 µM 4-Aminopyridine ActD: 25 µM actinomycin D
2014-03-12 | E-GEOD-55780 | biostudies-arrayexpress
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. 12 hippocampal cell culture samples analysed, 3 coverslips pooled per sample. Treatments are as follows: Block: an inhibitor cocktail containing 50 µM D-APV, 40 µM CNQX, and 100 nM TTX for 3 hrs Activity: 50 µM bicuculline (BiC)/500 µM 4-Aminopyridine ActD: 25 µM actinomycin D
2014-03-12 | E-GEOD-55778 | biostudies-arrayexpress
Project description:Spinocerebellar ataxia type 3 (SCA3/MJD) has a polyQ etiology but, the current knowledge on molecular processes and proteins involved in pathogenesis is insufficient. Due to its proteolytic function, Ataxin-3 can influence other proteins, yet the global picture of crucial proteins and pathways in SCA3 was not investigated previously. Here, we explored molecular SCA3 mechanism by interdisciplinary research paradigm combining SCA3 knock-in model, behavior, MRI, brain proteomics, precise axonal proteomics, neuronal energy recordings, labeling of vesicles, and inclusions and focusing in axonal compartment. Using the global proteomics, we found dysregulation of protein homeostasis over the entire disease progression. The early SCA3 phase was associated with reduced body weight gain, the presence of the number of dysregulated proteins related to metabolism and mitochondria, and an altered profile of oxygen consumption rate in neurons. Moreover, the early phase presented alterations of protein metabolism, cytoskeletal architecture, axonal and synaptic proteins. Protein dysregulations indicated that the compartment involved in SCA3 pathogenesis next to the mitochondria are also neuronal processes and axons in particular. To confirm that the axon is one of the central compartments in SCA3 pathogenesis, we performed targeted proteomics on axons and somatodendritic compartments. We revealed highly increased axonal localization of protein synthesis machinery, including ribosomes, translation factors, and RNA binding proteins, while the level of proteins responsible for cellular transport and mitochondria was decreased. In summary, the SCA3 disease mechanism is based on the broad influence of mutant ataxin-3 on the neuronal proteome. Processes central in our SCA3 model include disturbed localization of proteins between axonal and somatodendritic compartment, early neuronal energy deficit, altered neuronal cytoskeletal structure, an overabundance of protein synthetic machinery in axons.
2021-04-08 | PXD024945 | Pride
Project description:Loss-of-function mutations in the depalmitoylating enzyme palmitoyl protein thioesterase 1 (PPT1) cause Neuronal Ceroid Lipofuscinosis (NCL), a devastating neurodegenerative disease. The substrates of PPT1 are largely undescribed, posing a limitation on molecular dissection of disease mechanisms and therapeutic development. Here, we provide a resource identifying >100 novel PPT1 substrates. We utilized Acyl Resin-Assisted Capture and mass spectrometry to identify proteins with increased in vivo palmitoylation in PPT1 knockout mouse brains. We then validated putative substrates through direct depalmitoylation with recombinant PPT1. This stringent screen elucidated diverse PPT1 substrates at the synapse, including channels and transporters, G-protein-associated molecules, endo/exocytic components, synaptic adhesion molecules, and mitochondrial proteins. Cysteine depalmitoylation sites in transmembrane PPT1 substrates frequently participate in disulfide bonds in the mature protein. We confirmed that depalmitoylation plays a role in disulfide bond formation in a tertiary screen analyzing post-translational modifications. Collectively, these data highlight the role of PPT1 in mediating synapse functions, implicate molecular pathways in the etiology of NCL and other neurodegenerative diseases, and advance our basic understanding of the purpose of depalmitoylation.
2022-03-07 | PXD032052 | Pride