| Heat nociception (1) | CG31386
| CG31386 | | 0.38 |
none
| yes |
ReferenceA genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene. Neely et al.,
2010
Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the α2δ family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in α2δ3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.
Screen detailsStable Id:
GR00135-A-1
Screen title:
Heat nociception (1)
Assay:
Noxious heat avoidance and viability
Method:
Fly count
Scope:
Genome-wide
Screen type:
in vivo
Species:
Drosophila melanogaster
Biosource:
Organism
Biomodel:
elav-GAL4
Library:
VDRC, np
Reagent type:
UAS-IR construct
Score type:
Z-score
Cutoff:
> 1.65
Notes:
Additional information about secondary screens (geotactic, phototaxis, and temperature sensitivity)
|
| Lipid storage | FBgn0051386
| CG31386 | np | moderate |
Smaller sized lipid droplets, more dispersed
| no |
ReferenceFunctional genomic screen reveals genes involved in lipid-droplet formation and utilization. Guo et al.,
2008
Eukaryotic cells store neutral lipids in cytoplasmic lipid droplets enclosed in a monolayer of phospholipids and associated proteins. These dynamic organelles serve as the principal reservoirs for storing cellular energy and for the building blocks for membrane lipids. Excessive lipid accumulation in cells is a central feature of obesity, diabetes and atherosclerosis, yet remarkably little is known about lipid-droplet cell biology. Here we show, by means of a genome-wide RNA interference (RNAi) screen in Drosophila S2 cells that about 1.5% of all genes function in lipid-droplet formation and regulation. The phenotypes of the gene knockdowns sorted into five distinct phenotypic classes. Genes encoding enzymes of phospholipid biosynthesis proved to be determinants of lipid-droplet size and number, suggesting that the phospholipid composition of the monolayer profoundly affects droplet morphology and lipid utilization. A subset of the Arf1-COPI vesicular transport proteins also regulated droplet morphology and lipid utilization, thereby identifying a previously unrecognized function for this machinery. These phenotypes are conserved in mammalian cells, suggesting that insights from these studies are likely to be central to our understanding of human diseases involving excessive lipid storage.
Screen detailsStable Id:
GR00090-A-0
Screen title:
Lipid storage
Assay:
Lipid droplet staining
Method:
High content (microscopy)
Scope:
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
S2
Library:
, OpenBiosystems
Reagent type:
dsRNA
Score type:
Visual inspection
Cutoff:
np
Notes:
|
| Lipid storage | FBgn0051386
| | | -0.05 |
none
| no |
ReferenceCOPI complex is a regulator of lipid homeostasis. Beller et al.,
2008
Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa) protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi) screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI) transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL) with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets.
Screen detailsStable Id:
GR00002-A-0
Screen title:
Lipid storage
Assay:
Lipid droplet staining
Method:
High content (microscopy)
Scope:
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
Kc167
Library:
, DRSC
Reagent type:
dsRNA
Score type:
B-score
Cutoff:
2.0 / -1.7
Notes:
|
| PGN-induced dJNK phosphorylation | FBgn0051386
| CG31386 | np | 4.18 |
Increased P-JNK protein expression with PGN
| no |
ReferenceA quantitative RNAi screen for JNK modifiers identifies Pvr as a novel regulator of Drosophila immune signaling. Bond and Foley,
2009
Drosophila melanogaster responds to gram-negative bacterial challenges through the IMD pathway, a signal transduction cassette that is driven by the coordinated activities of JNK, NF-kappaB and caspase modules. While many modifiers of NF-kappaB activity were identified in cell culture and in vivo assays, the regulatory apparatus that determines JNK inputs into the IMD pathway is relatively unexplored. In this manuscript, we present the first quantitative screen of the entire genome of Drosophila for novel regulators of JNK activity in the IMD pathway. We identified a large number of gene products that negatively or positively impact on JNK activation in the IMD pathway. In particular, we identified the Pvr receptor tyrosine kinase as a potent inhibitor of JNK activation. In a series of in vivo and cell culture assays, we demonstrated that activation of the IMD pathway drives JNK-dependent expression of the Pvr ligands, Pvf2 and Pvf3, which in turn act through the Pvr/ERK MAP kinase pathway to attenuate the JNK and NF-kappaB arms of the IMD pathway. Our data illuminate a poorly understood arm of a critical and evolutionarily conserved innate immune response. Furthermore, given the pleiotropic involvement of JNK in eukaryotic cell biology, we believe that many of the novel regulators identified in this screen are of interest beyond immune signaling.
Screen detailsStable Id:
GR00148-A
Screen title:
PGN-induced dJNK phosphorylation
Assay:
P-JNK protein expression
Method:
Fluorescence
Scope:
Genome-wide
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
S2
Library:
Open Biosystems and custom-made, np and custom-made
Reagent type:
dsRNA
Score type:
Z-score
Cutoff:
Complex criteria
Notes:
Only hits stored in GenomeRNAi
|
| Lipid storage | FBgn0051386
| | | 0.56 |
none
| no |
ReferenceCOPI complex is a regulator of lipid homeostasis. Beller et al.,
2008
Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa) protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi) screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI) transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL) with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets.
Screen detailsStable Id:
GR00002-A-0
Screen title:
Lipid storage
Assay:
Lipid droplet staining
Method:
High content (microscopy)
Scope:
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
Kc167
Library:
, DRSC
Reagent type:
dsRNA
Score type:
B-score
Cutoff:
2.0 / -1.7
Notes:
|
| Cell size and cell-cycle regulation (1) | FBgn0051386
| CG31386 | HL01958 | sp |
none
| no |
ReferenceIdentification of pathways regulating cell size and cell-cycle progression by RNAi. Bjӧrklund et al.,
2006
Many high-throughput loss-of-function analyses of the eukaryotic cell cycle have relied on the unicellular yeast species Saccharomyces cerevisiae and Schizosaccharomyces pombe. In multicellular organisms, however, additional control mechanisms regulate the cell cycle to specify the size of the organism and its constituent organs. To identify such genes, here we analysed the effect of the loss of function of 70% of Drosophila genes (including 90% of genes conserved in human) on cell-cycle progression of S2 cells using flow cytometry. To address redundancy, we also targeted genes involved in protein phosphorylation simultaneously with their homologues. We identify genes that control cell size, cytokinesis, cell death and/or apoptosis, and the G1 and G2/M phases of the cell cycle. Classification of the genes into pathways by unsupervised hierarchical clustering on the basis of these phenotypes shows that, in addition to classical regulatory mechanisms such as Myc/Max, Cyclin/Cdk and E2F, cell-cycle progression in S2 cells is controlled by vesicular and nuclear transport proteins, COP9 signalosome activity and four extracellular-signal-regulated pathways (Wnt, p38betaMAPK, FRAP/TOR and JAK/STAT). In addition, by simultaneously analysing several phenotypes, we identify a translational regulator, eIF-3p66, that specifically affects the Cyclin/Cdk pathway activity.
Screen detailsStable Id:
GR00048-A-1
Screen title:
Cell size and cell-cycle regulation (1)
Assay:
Cell size, DNA content and viability
Method:
Flow cytometry
Scope:
Kinases, phosphatases and selected genes
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
S2
Library:
Custom-made, DGC1, DGC2 and PHOSPHO
Reagent type:
dsRNA
Score type:
Complex, sp
Cutoff:
Complex criteria
Notes:
Additional information about the primary sccreen (pooled library) and a secondary screen (number of binucleate cells)
|
| Cell size and cell-cycle regulation (1) | FBgn0051386
| CG31386 | RE39877 | sp |
none
| no |
ReferenceIdentification of pathways regulating cell size and cell-cycle progression by RNAi. Bjӧrklund et al.,
2006
Many high-throughput loss-of-function analyses of the eukaryotic cell cycle have relied on the unicellular yeast species Saccharomyces cerevisiae and Schizosaccharomyces pombe. In multicellular organisms, however, additional control mechanisms regulate the cell cycle to specify the size of the organism and its constituent organs. To identify such genes, here we analysed the effect of the loss of function of 70% of Drosophila genes (including 90% of genes conserved in human) on cell-cycle progression of S2 cells using flow cytometry. To address redundancy, we also targeted genes involved in protein phosphorylation simultaneously with their homologues. We identify genes that control cell size, cytokinesis, cell death and/or apoptosis, and the G1 and G2/M phases of the cell cycle. Classification of the genes into pathways by unsupervised hierarchical clustering on the basis of these phenotypes shows that, in addition to classical regulatory mechanisms such as Myc/Max, Cyclin/Cdk and E2F, cell-cycle progression in S2 cells is controlled by vesicular and nuclear transport proteins, COP9 signalosome activity and four extracellular-signal-regulated pathways (Wnt, p38betaMAPK, FRAP/TOR and JAK/STAT). In addition, by simultaneously analysing several phenotypes, we identify a translational regulator, eIF-3p66, that specifically affects the Cyclin/Cdk pathway activity.
Screen detailsStable Id:
GR00048-A-1
Screen title:
Cell size and cell-cycle regulation (1)
Assay:
Cell size, DNA content and viability
Method:
Flow cytometry
Scope:
Kinases, phosphatases and selected genes
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
S2
Library:
Custom-made, DGC1, DGC2 and PHOSPHO
Reagent type:
dsRNA
Score type:
Complex, sp
Cutoff:
Complex criteria
Notes:
Additional information about the primary sccreen (pooled library) and a secondary screen (number of binucleate cells)
|
| Heat nociception (1) | CG31386
| CG31386 | | -0.29 |
none
| yes |
ReferenceA genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene. Neely et al.,
2010
Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the α2δ family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in α2δ3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.
Screen detailsStable Id:
GR00135-A-1
Screen title:
Heat nociception (1)
Assay:
Noxious heat avoidance and viability
Method:
Fly count
Scope:
Genome-wide
Screen type:
in vivo
Species:
Drosophila melanogaster
Biosource:
Organism
Biomodel:
elav-GAL4
Library:
VDRC, np
Reagent type:
UAS-IR construct
Score type:
Z-score
Cutoff:
> 1.65
Notes:
Additional information about secondary screens (geotactic, phototaxis, and temperature sensitivity)
|
| Lipid storage | FBgn0051386
| | | 0.05 |
none
| no |
ReferenceCOPI complex is a regulator of lipid homeostasis. Beller et al.,
2008
Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa) protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi) screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI) transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL) with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets.
Screen detailsStable Id:
GR00002-A-0
Screen title:
Lipid storage
Assay:
Lipid droplet staining
Method:
High content (microscopy)
Scope:
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
Kc167
Library:
, DRSC
Reagent type:
dsRNA
Score type:
B-score
Cutoff:
2.0 / -1.7
Notes:
|
| Lipid storage | FBgn0051386
| | | -0.32 |
none
| no |
ReferenceCOPI complex is a regulator of lipid homeostasis. Beller et al.,
2008
Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa) protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi) screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI) transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL) with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets.
Screen detailsStable Id:
GR00002-A-0
Screen title:
Lipid storage
Assay:
Lipid droplet staining
Method:
High content (microscopy)
Scope:
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
Kc167
Library:
, DRSC
Reagent type:
dsRNA
Score type:
B-score
Cutoff:
2.0 / -1.7
Notes:
|
