Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of RNAi-mediated knockdown of cac on gene expression in motor neurons of Drosophila melanogaster third instar larva

ABSTRACT: Entry of calcium into the terminal bouton of a neuron is critical step in action potential-dependent neurotransmitter release. At the Drosophila larval neuromuscular junction, the conversion of the presynaptic motor neuron’s electrical activity into a chemical signal is mediated by the voltage-gated calcium channel Cacophony (Cac). While RNAi knockdown of cac dramatically reduces the probability of evoked neurotransmitter release at the NMJ, locomotion remains largely unaffected (Hoagland et al., 2025). Here we investigate the mechanism of this compensation by sequencing the transcriptomes of Cac RNAi motor neurons. We find decreased expression of K+ channels as seen with the Rbp or unc-13 knockdown models of presynaptic dysfunction.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE301255 | GEO | 2025/07/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Active forgetting requires Sickie function in a dedicated dopamine circuit in Drosophila

Project description:Forgetting is an essential component of the brain memory management system, providing a balance to memory formation processes by removing unused or unwanted memories, or by suppressing their expression. However, the molecular, cellular and circuit mechanisms underlying forgetting are poorly understood. Here we show that the memory suppressor gene, sickie, functions in a single dopamine neuron (DAn) by supporting the process of active forgetting in Drosophila. RNAi knockdown (KD) of sickie impairs forgetting by reducing the Ca2+ influx and DA release from the DAn that promotes forgetting. Co-immunoprecipitation/mass spectrometry analyses identified cytoskeletal and presynaptic active zone (AZ) proteins as candidates that physically interact with Sickie, and a focused RNAi screen of the candidates showed that Bruchpilot (Brp), a presynaptic AZ protein that regulates calcium channel clustering and neurotransmitter release, impairs active forgetting like sickie KD. In addition, overexpression of brp rescued the impaired forgetting of sickie KD, providing evidence that they function in the same process. Moreover, we show that sickie KD in the DAn reduces the abundance and size of AZ markers but increases their number, suggesting that Sickie controls DAn activity for forgetting by modulating the presynaptic AZ structure. Our results identify a new molecular and circuit mechanism for normal levels of active forgetting and reveal a surprising role of Sickie in maintaining presynaptic AZ structure for neurotransmitter release.

2022-08-13 | MSV000090127 | MassIVE

The long noncoding RNA neuroLNC modulates neurotransmitter release interacting with a neurodegeneration-associated protein

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

The temporal profile of activity-dependent presynaptic phospho-signalling reveals a PP1-dependent reduction in vesicle release

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

Pre- and postsynaptic MEF2C promote experience-dependent, input-specific development of Layer 4 to Layer 2/3 excitatory synapses

Project description:Experience and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here we provide evidence that the activity-dependent transcription factor Myocyte-Enhancer Factor 2C (MEF2C) is required in both presynaptic layer 4 (L4) and postsynaptic L2/3 somatosensory (S1) cortical neurons for development of their synaptic connection. In contrast, synaptic inputs from local L2/3, contralateral S1, or ipsilateral frontal/motor cortex are unaffected by postsynaptic Mef2c deletion in L2/3 neurons. Postsynaptic MEF2C is required for L4 to L2/3 synapse function during, but not after, an early postnatal, experience-dependent period. Furthermore, homozygous and heterozygous Mef2c deletion in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Our results suggested that experience or activity-dependent transcriptional activation of MEF2C promotes development of L4→L2/3 synapses. In support of this idea, expression of transcriptionally active MEF2C (MEF2C-VP16) rescued weak L4 to L2/3 synaptic strength in sensory deprived mice. Consistent with a presynaptic function for MEF2C, we find that MEF2C regulates the activity-dependent expression of many presynaptic assembly genes, including transsynaptic cell adhesion proteins and regulators of neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.

2025-01-17 | GSE253629 | GEO

Atherosclerotic environment effect over CAC pre-angiogenic role

Project description:In response to vascular injury, early EPC or Circulating angiogenic cells (CAC) are thought to be recruited to the damaged areas, participating mainly in a paracrine fashion, by releasing pro-angiogenic factors, promoting the mobilization of other cell populations such as the late EPC, or endothelial colony-forming cells (ECFC). ECFC will help by replacing the damaged endothelium and promoting neovascularization. Unfortunately, however, despite the regenerative role, the number and function of EPC are severely affected under pathological conditions, making compulsory to better understand how these cells react under those environments in order to implement their use in regenerative cell therapies. Herein we evaluated, for the first time to our knowledge, the effect of atherosclerotic factors over the paracrine role of CAC, by direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. The application of a label free proteomics approach allowed the identification of 194 altered proteins in the secretome of pre-conditioned CAC, many of them related, among others, with inhibition of angiogenesis and cell migration. Functional assays corroborated that, after atherosclerotic pre-conditioning, the pro-angiogenic effect of CAC over ECFC was impaired, affecting ECFC migration as well as their ability to form tubules on a basement membrane matrix assay. Up-regulation of several anti-angiogenic proteins in the CAC secretome could help to explain such angiogenic switch which, in turns, could reflect a protective and beneficial effect against the atherosclerotic process.

2021-09-09 | PXD019395 | Pride

The temporal profile of activity-dependent presynaptic phospho-signalling reveals long lasting patterns of post-stimulus regulation

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 activity-dependent phospho-signalling, which includes two KCl stimulation levels and analysis of the post-stimulus period. We profiled 1,917 regulated phosphopeptides and bioinformatically identified six temporal patterns of co-regulated proteins. The presynaptic proteins with large changes in phospho-status were again prominently regulated in the analysis of 7,070 activity-dependent phosphopeptides from KCl-stimulated cultured hippocampal neurons. Active zone scaffold proteins showed a high level of activity-dependent phospho-regulation that far exceeded the response from postsynaptic density scaffold proteins. Accordingly, bassoon was identified as the major target of neuronal phospho-signalling. We developed a probabilistic computational method, KinSwing, which matched protein kinase substrate motifs to regulated phosphorylation sites to reveal underlying protein kinase activity. This approach allowed us to link protein kinases to profiles of co-regulated presynaptic protein networks. CaMKIIα responded rapidly, scaled with stimulus strength and had long-lasting activity. MAPK/ERK was the main protein kinase predicted to control a distinct and significant pattern of post-stimulus up-regulation of phosphorylation. This work provides a unique resource of activity-dependent phosphorylation sites of synaptosomes and neurons, the vast majority of which have not been investigated with regard to their functional impact. This resource will enable detailed characterization of the phospho-regulated mechanisms impacting the plasticity of neurotransmitter release.

2019-01-28 | PXD010007 | Pride

Effect of RNAi-mediated knockdown of cac on gene expression in motor neurons of Drosophila melanogaster third instar larva

Project description:Effect of RNAi-mediated knockdown of cac on gene expression in motor neurons of Drosophila melanogaster third instar larva

| PRJNA1284346 | ENA

Phosphoproteomic analysis of mouse neurons with SRPK2 overexpression or knockdown

Project description:SRPK2 was identified as a presynaptic protein kinase involved in the regulation of neurotransmitter release. The phosphoproteome of mouse primary neurons was screened, under the conditions of SRPK2 overexpression and SRPK2 knockdown, to identify candidate substrates of SRPK2.

2022-02-14 | PXD016636 | Pride

Effect of RNAi-mediated knockdown of unc-13 and Rbp on gene expression in motor neurons of Drosophila melanogaster third instar larva

Project description:Reliable neurotransmission is dependent on coordinating entry of calcium into the terminal boutons of a presynaptic neuron with the exocytosis of vesicles into the synaptic cleft. This function fulfilled by an assembly of proteins in a specialized region of the presynaptic plasma membrane called the active zone (AZ). Here we use the fruit fly neuromuscular junction as a model synapse to test the consequences of specific depletion of two key AZ proteins, unc-13 and RIM-binding protein (Rbp), by RNAi knockdown on the transcriptome of these motor neurons. We find that decreased expression of Rbp results in concomittant decrease of expression in unc-13 and that the sets of differentially expressed genes between the two knockdowns are highly similar. We show that these knockdowns result in increased expression of genes involved in neuropeptide signalling, while reducing expression of other genes encoding the components of the AZ and voltage-gated K+ channels. Taken together, our findings suggest that knockdown of AZ components results in gene expression changes that bias the presynaptic neuron towards increased firing to compensate for the loss of AZs.

2024-08-28 | GSE250462 | GEO

Transcriptome profiling of Drosophila motor neurons with age

Project description:The purpose of this array was to investigate age-dependent changes the transcriptome of a highly homogenous cell population (Drosophila motor neurons) in order to help understand the contribution of changes in gene expression to age-dependent motor deficiencies. Drosophila motor neurons expressing GFP (via the UAS-Gal4 binary expression system) were isolated using flow cytometry from flies that were 7, 35 or 45 days old. The microarray design was highly redundant for calcium-binding and ion channel genes as we had apriori reasons to believe changes in these genes would be important. The ages were chosen because previous work had identified a major shift in neurotransmitter release between the ages of 35 and 45 days in Drosophila motor neurons. Although no significant changes were identified in that window, several genes showed elevated expression in old (35 day and 45 day) motor neurons compared to young (7 day) including matrix metalloproteinase 1 (dMMP1).

2017-11-08 | GSE106632 | GEO

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