Analysis of a long noncoding RNAs that modulate neurotransmitter release
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD013434
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE131103 | GEO | 2020/04/10
REPOSITORIES: GEO
Similar Datasets
Project description:The roles of long noncoding RNAs (lncRNAs) in synaptic transmission and neuronal development are emerging. Here we applied an integrated bioinformatic/biological screening strategy to identify lncRNAs that regulate synaptic vesicle release. We identified neuroLNC, a conserved neuron-specific nuclear lncRNA that modulates synaptic vesicle release, presynaptic calcium influx, neurite elongation and neuronal migration. In neurons neuroLNC interacts with a neurodegeneration-associated protein and tunes a set of presynaptic transcripts implicated in neurotransmitter release.
2020-05-26 | PXD013434 | Pride
Project description:Little is known about transcriptional control of neurite branching or presynaptic differentiation, events that occur relatively late in neuronal development. Using the C. elegans mechanosensory circuit as an in vivo model, we show that SAM-10, an ortholog of mammalian Single-Stranded DNA binding Protein (SSDP), functions cell-autonomously in the nucleus to regulate synaptic differentiation as well as positioning of a single neurite branch. PLM mechanosensory neurons in sam-10 mutants exhibit abnormal placement of the neurite branch point, and defective synaptogenesis, characterized by an overextended synaptic varicosity, underdeveloped synaptic morphology and disrupted co-localization of active zone and synaptic vesicles. SAM-10 functions coordinately with LDB-1 (Lim Domain Binding protein-1), demonstrated by our observations that 1) mutations in either gene show similar defects in PLM neurons; and 2) LDB-1 is required for SAM-10 nuclear localization. SAM-10 regulates PLM synaptic differentiation by suppressing transcription of prk-2, which encodes an ortholog of the mammalian Pim kinase family. PRK-2-mediated activities of SAM-10 are specifically involved in PLM synaptic differentiation, but not other sam-10 phenotypes such as neurite branching. Thus, these data reveal a novel transcriptional signaling pathway that regulates neuronal specification of neurite branching and presynaptic differentiation.
2010-11-12 | GSE25285 | GEO
Project description:Little is known about transcriptional control of neurite branching or presynaptic differentiation, events that occur relatively late in neuronal development. Using the C. elegans mechanosensory circuit as an in vivo model, we show that SAM-10, an ortholog of mammalian Single-Stranded DNA binding Protein (SSDP), functions cell-autonomously in the nucleus to regulate synaptic differentiation as well as positioning of a single neurite branch. PLM mechanosensory neurons in sam-10 mutants exhibit abnormal placement of the neurite branch point, and defective synaptogenesis, characterized by an overextended synaptic varicosity, underdeveloped synaptic morphology and disrupted co-localization of active zone and synaptic vesicles. SAM-10 functions coordinately with LDB-1 (Lim Domain Binding protein-1), demonstrated by our observations that 1) mutations in either gene show similar defects in PLM neurons; and 2) LDB-1 is required for SAM-10 nuclear localization. SAM-10 regulates PLM synaptic differentiation by suppressing transcription of prk-2, which encodes an ortholog of the mammalian Pim kinase family. PRK-2-mediated activities of SAM-10 are specifically involved in PLM synaptic differentiation, but not other sam-10 phenotypes such as neurite branching. Thus, these data reveal a novel transcriptional signaling pathway that regulates neuronal specification of neurite branching and presynaptic differentiation. Animals were grown on fresh 8P plates (Wormbook.org) until gravid. Eggs were collected by bleaching and hatched in M9 buffer overnight. L1 animals were fed on fresh food for 2 hours at room temperature, harvested and separated from worm debris using a 25μm mesh. RNA was isolated using a standard Trizol protocol. RNA preps were stored at -80C. Quality of RNA preps was first estimated using Agilent 2100 Bioanalyzer. RNA was then reverse-transcribed using the Genisphere Array 350 kit, which generate tagged cDNA. Resulted products are hybridized to the microarrays. Four independent high quality RNA preps (RIN>=7) were chosen for microarray assay using long oligomer-based spotted microarray (Washington University, St. Louis, MO). For dye-swap controls, we ran a technical replicate hybridization for each pair of samples in which the dyes are reversed. Gene spots with “found/good” signals (defined by ScanArray, channel flag 3) in all scans were chosen for gene expression analysis.
2010-11-12 | E-GEOD-25285 | biostudies-arrayexpress
Project description:Epithelial-neuronal signaling is essential for sensory encoding in touch, itch and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as framework to directly test this hypothesis. RNA sequencing of adult Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission. Moreover, live-cell imaging directly demonstrated that Merkel cells mediate activity- and VMAT-dependent release of fluorescent catecholamine neurotransmitter analogues. Touch-evoked firing in Merkel-cell afferents was inhibited either by pre-synaptic silencing of SNARE-mediated vesicle release from Merkel cells or by neuronal deletion of b2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch.
2018-11-08 | GSE114336 | GEO
Project description:Network hyperexcitability is manifested as frequent ictal discharges, often caused by unbalanced neurotransmission. We assessed synaptic changes in the hyperexcitable visual cortex of tetanus neurotoxin-injected mice (TeNT). A proteomics analysis of synaptic content revealed Carboxypeptidase E (CPE) up-regulation following TeNT injection. To quantify CPE effect on vesicle clustering, we used an ultrastructural measure of synaptic activity to investigate functional differences at excitatory and inhibitory synapses. We found homeostatic changes in hyperexcitable networks expressed as an early onset lengthening of active zones at inhibitory synapses followed by spatial reorganization at excitatory synapses. Moreover, inhibition of CPE decreases ictal discharges in vivo. This study reveals a complex landscape of homeostatic changes affecting the synaptic release machinery , differentially at inhibitory and excitatory terminals. We propose a novel homeostatic presynaptic mechanism which may impact release timing rather than synaptic strength.
2021-09-09 | PXD022270 | Pride
Project description:Depolarization of presynaptic terminals stimulates calcium influx, which evokes neurotransmitter release and activates phosphorylation-based signalling. Here, we present the first global temporal profile of presynaptic proteins undergoing post-stimulus phospho-signalling to reveal long-lasting changes, key substrates and master regulators. A total of 5,715 unique phosphopeptides from 1,817 proteins were profiled and 1,917 phosphopeptides had activity-dependent phosphorylation sites. A new computational method, KinSwing, combining protein kinase substrate prediction and activity across time, enabled the prediction of effector protein kinase activity. CaMKII responded rapidly to depolarization. MAPK, CDK5 and GSK3β had a post-stimulus role in compensating for initial dephosphorylation. Despite this, the post-stimulus period was dominated by down-regulation of phosphorylation and was exacerbated by conditions stimulating increased calcium influx. Down-regulated phosphorylation correlated with perturbed phospho-signalling to protein phosphatase 1 (PP1) regulatory molecules and reduced glutamate and fluorescent dye release. Inhibition PP1 prevented reduction in dye release, identifying PP1 as a major signalling target and mediator of post-stimulus presynaptic phospho-signalling.
2019-01-24 | PXD008495 | Pride
Project description:Synaptic plasticity has been shown to participate in control of energy homeostasis.The paraventricular hypothalamus (PVH) is crucial for satiety control, though the underlying synaptic mechanisms remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 leads to hyperphagic obesity. We further show that KO of PVH RUVBL2 impairs the excitatory synaptic transmission by reducing presynaptic boutons and altering synaptic vesicle distribution. Chromatin immunoprecipitation-sequencing (ChlP-seq) data show that RUVBL2 binds to the promoters of numerous genes related to synaptic plasticity, in particular synaptic vesicle and neuron axonogenesis. Meanwhile, RNA-seq data show significant changes in the expression of some genes in these two pathways. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulating synaptic plasticity could be an effective way to curb appetite and obesity.
2024-10-02 | GSE252308 | GEO
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
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-9211 | biostudies-arrayexpress
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-9212 | biostudies-arrayexpress