| Heat nociception (1) | CG12666
| CG32704 | | -1.17 |
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)
|
| Heat nociception (1) | CG12122
| CG32704 | | -1.17 |
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 | FBgn0052704
| | | 0.09 |
Lipid understorage
| 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:
|
| Ca2+ signaling | FBgn0052704
| CG12122 | np | np |
none
| no |
ReferenceSTIM1, an essential and conserved component of store-operated Ca2+ channel function. Roos et al.,
2005
Store-operated Ca2+ (SOC) channels regulate many cellular processes, but the underlying molecular components are not well defined. Using an RNA interference (RNAi)-based screen to identify genes that alter thapsigargin (TG)-dependent Ca2+ entry, we discovered a required and conserved role of Stim in SOC influx. RNAi-mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG-dependent Ca2+ entry. Patch-clamp recording revealed nearly complete suppression of the Drosophila Ca2+ release-activated Ca2+ (CRAC) current that has biophysical characteristics similar to CRAC current in human T cells. Similarly, knockdown of the human homologue STIM1 significantly reduced CRAC channel activity in Jurkat T cells. RNAi-mediated knockdown of STIM1 inhibited TG- or agonist-dependent Ca2+ entry in HEK293 or SH-SY5Y cells. Conversely, overexpression of STIM1 in HEK293 cells modestly enhanced TG-induced Ca2+ entry. We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels.
Screen detailsStable Id:
GR00061-A-0
Screen title:
Ca2+ signaling
Assay:
Store-operated calcium entry
Method:
Fluorescence
Scope:
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
S2 cells
Library:
, Custom-made library
Reagent type:
dsRNA
Score type:
np
Cutoff:
np
Notes:
|
| Cell growth and viability (1) |
| | | 0 |
none
| yes |
ReferenceGenome-wide RNAi analysis of growth and viability in Drosophila cells. Boutros et al.,
2004
A crucial aim upon completion of whole genome sequences is the functional analysis of all predicted genes. We have applied a high-throughput RNA-interference (RNAi) screen of 19,470 double-stranded (ds) RNAs in cultured cells to characterize the function of nearly all (91%) predicted Drosophila genes in cell growth and viability. We found 438 dsRNAs that identified essential genes, among which 80% lacked mutant alleles. A quantitative assay of cell number was applied to identify genes of known and uncharacterized functions. In particular, we demonstrate a role for the homolog of a mammalian acute myeloid leukemia gene (AML1) in cell survival. Such a systematic screen for cell phenotypes, such as cell viability, can thus be effective in characterizing functionally related genes on a genome-wide scale.
Screen detailsStable Id:
GR00031-A-1
Screen title:
Cell growth and viability (1)
Assay:
Cell number and viability
Method:
Luminescence
Scope:
Genome-wide
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
Kc167
Library:
Custom-made, HFA
Reagent type:
dsRNA
Score type:
Z-score
Cutoff:
>= 3.0
Notes:
|
| Lipid storage | FBgn0052704
| | | -1.54 |
Lipid understorage
| 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 | FBgn0052704
| | | 1.75 |
Lipid understorage
| 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 growth and viability (1) |
| | | -0.2 |
none
| yes |
ReferenceGenome-wide RNAi analysis of growth and viability in Drosophila cells. Boutros et al.,
2004
A crucial aim upon completion of whole genome sequences is the functional analysis of all predicted genes. We have applied a high-throughput RNA-interference (RNAi) screen of 19,470 double-stranded (ds) RNAs in cultured cells to characterize the function of nearly all (91%) predicted Drosophila genes in cell growth and viability. We found 438 dsRNAs that identified essential genes, among which 80% lacked mutant alleles. A quantitative assay of cell number was applied to identify genes of known and uncharacterized functions. In particular, we demonstrate a role for the homolog of a mammalian acute myeloid leukemia gene (AML1) in cell survival. Such a systematic screen for cell phenotypes, such as cell viability, can thus be effective in characterizing functionally related genes on a genome-wide scale.
Screen detailsStable Id:
GR00031-A-1
Screen title:
Cell growth and viability (1)
Assay:
Cell number and viability
Method:
Luminescence
Scope:
Genome-wide
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
Kc167
Library:
Custom-made, HFA
Reagent type:
dsRNA
Score type:
Z-score
Cutoff:
>= 3.0
Notes:
|
| Cell growth and viability (2) |
| | | 0.1 |
none
| no |
ReferenceGenome-wide RNAi analysis of growth and viability in Drosophila cells. Boutros et al.,
2004
A crucial aim upon completion of whole genome sequences is the functional analysis of all predicted genes. We have applied a high-throughput RNA-interference (RNAi) screen of 19,470 double-stranded (ds) RNAs in cultured cells to characterize the function of nearly all (91%) predicted Drosophila genes in cell growth and viability. We found 438 dsRNAs that identified essential genes, among which 80% lacked mutant alleles. A quantitative assay of cell number was applied to identify genes of known and uncharacterized functions. In particular, we demonstrate a role for the homolog of a mammalian acute myeloid leukemia gene (AML1) in cell survival. Such a systematic screen for cell phenotypes, such as cell viability, can thus be effective in characterizing functionally related genes on a genome-wide scale.
Screen detailsStable Id:
GR00031-A-2
Screen title:
Cell growth and viability (2)
Assay:
Cell number and viability
Method:
Luminescence
Scope:
Genome-wide
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
S2R+
Library:
Custom-made, HFA
Reagent type:
dsRNA
Score type:
Z-score
Cutoff:
>= 3.0
Notes:
|
| Lipid storage | FBgn0052704
| | | -0.51 |
Lipid understorage
| 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:
|
| Notch pathway regulation (4) | CG32704
| | | 0 |
none
| no |
ReferenceGenome-wide analysis of Notch signalling in Drosophila by transgenic RNAi. Mummery-Widmer et al.,
2009
Genome-wide RNA interference (RNAi) screens have identified near-complete sets of genes involved in cellular processes. However, this methodology has not yet been used to study complex developmental processes in a tissue-specific manner. Here we report the use of a library of Drosophila strains expressing inducible hairpin RNAi constructs to study the Notch signalling pathway during external sensory organ development. We assigned putative loss-of-function phenotypes to 21.2% of the protein-coding Drosophila genes. Using secondary assays, we identified 6 new genes involved in asymmetric cell division and 23 novel genes regulating the Notch signalling pathway. By integrating our phenotypic results with protein interaction data, we constructed a genome-wide, functionally validated interaction network governing Notch signalling and asymmetric cell division. We used clustering algorithms to identify nuclear import pathways and the COP9 signallosome as Notch regulators. Our results show that complex developmental processes can be analysed on a genome-wide level and provide a unique resource for functional annotation of the Drosophila genome.
Screen detailsStable Id:
GR00144-A-4
Screen title:
Notch pathway regulation (4)
Assay:
External sensory organ morphology and viability
Method:
Visual inspection
Scope:
Genome-wide
Screen type:
in vivo
Species:
Drosophila melanogaster
Biosource:
Tissue
Biomodel:
pnr-GAL4
Library:
VDRC, np
Reagent type:
UAS-IR construct
Score type:
Phenotype strength
Cutoff:
np
Notes:
|
| Muscle morphogenesis and function (1) | CG32704
| CG32704 | | np |
none
| no |
ReferenceSystematic genetic analysis of muscle morphogenesis and function in Drosophila. Schnorrer et al.,
2010
Systematic genetic approaches have provided deep insight into the molecular and cellular mechanisms that operate in simple unicellular organisms. For multicellular organisms, however, the pleiotropy of gene function has largely restricted such approaches to the study of early embryogenesis. With the availability of genome-wide transgenic RNA interference (RNAi) libraries in Drosophila, it is now possible to perform a systematic genetic dissection of any cell or tissue type at any stage of the lifespan. Here we apply these methods to define the genetic basis for formation and function of the Drosophila muscle. We identify a role in muscle for 2,785 genes, many of which we assign to specific functions in the organization of muscles, myofibrils or sarcomeres. Many of these genes are phylogenetically conserved, including genes implicated in mammalian sarcomere organization and human muscle diseases.
Screen detailsStable Id:
GR00134-A-1
Screen title:
Muscle morphogenesis and function (1)
Assay:
Posture, locomotion, flight and viability
Method:
Visual inspection
Scope:
Genome-wide
Screen type:
in vivo
Species:
Drosophila melanogaster
Biosource:
Tissue
Biomodel:
Mef2-GAL4
Library:
VDRC, np
Reagent type:
UAS-IR construct
Score type:
rp
Cutoff:
S19 > 0.5
Notes:
|
| Lipid storage | FBgn0052704
| | | -2.04 |
Lipid understorage
| 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:
|
| Muscle morphogenesis and function (1) | CG32704
| CG32704 | | np |
none
| no |
ReferenceSystematic genetic analysis of muscle morphogenesis and function in Drosophila. Schnorrer et al.,
2010
Systematic genetic approaches have provided deep insight into the molecular and cellular mechanisms that operate in simple unicellular organisms. For multicellular organisms, however, the pleiotropy of gene function has largely restricted such approaches to the study of early embryogenesis. With the availability of genome-wide transgenic RNA interference (RNAi) libraries in Drosophila, it is now possible to perform a systematic genetic dissection of any cell or tissue type at any stage of the lifespan. Here we apply these methods to define the genetic basis for formation and function of the Drosophila muscle. We identify a role in muscle for 2,785 genes, many of which we assign to specific functions in the organization of muscles, myofibrils or sarcomeres. Many of these genes are phylogenetically conserved, including genes implicated in mammalian sarcomere organization and human muscle diseases.
Screen detailsStable Id:
GR00134-A-1
Screen title:
Muscle morphogenesis and function (1)
Assay:
Posture, locomotion, flight and viability
Method:
Visual inspection
Scope:
Genome-wide
Screen type:
in vivo
Species:
Drosophila melanogaster
Biosource:
Tissue
Biomodel:
Mef2-GAL4
Library:
VDRC, np
Reagent type:
UAS-IR construct
Score type:
rp
Cutoff:
S19 > 0.5
Notes:
|
| Cell growth and viability (2) |
| | | -0.4 |
none
| no |
ReferenceGenome-wide RNAi analysis of growth and viability in Drosophila cells. Boutros et al.,
2004
A crucial aim upon completion of whole genome sequences is the functional analysis of all predicted genes. We have applied a high-throughput RNA-interference (RNAi) screen of 19,470 double-stranded (ds) RNAs in cultured cells to characterize the function of nearly all (91%) predicted Drosophila genes in cell growth and viability. We found 438 dsRNAs that identified essential genes, among which 80% lacked mutant alleles. A quantitative assay of cell number was applied to identify genes of known and uncharacterized functions. In particular, we demonstrate a role for the homolog of a mammalian acute myeloid leukemia gene (AML1) in cell survival. Such a systematic screen for cell phenotypes, such as cell viability, can thus be effective in characterizing functionally related genes on a genome-wide scale.
Screen detailsStable Id:
GR00031-A-2
Screen title:
Cell growth and viability (2)
Assay:
Cell number and viability
Method:
Luminescence
Scope:
Genome-wide
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
S2R+
Library:
Custom-made, HFA
Reagent type:
dsRNA
Score type:
Z-score
Cutoff:
>= 3.0
Notes:
|
| Notch pathway regulation (4) | CG32704
| | | 0 |
none
| no |
ReferenceGenome-wide analysis of Notch signalling in Drosophila by transgenic RNAi. Mummery-Widmer et al.,
2009
Genome-wide RNA interference (RNAi) screens have identified near-complete sets of genes involved in cellular processes. However, this methodology has not yet been used to study complex developmental processes in a tissue-specific manner. Here we report the use of a library of Drosophila strains expressing inducible hairpin RNAi constructs to study the Notch signalling pathway during external sensory organ development. We assigned putative loss-of-function phenotypes to 21.2% of the protein-coding Drosophila genes. Using secondary assays, we identified 6 new genes involved in asymmetric cell division and 23 novel genes regulating the Notch signalling pathway. By integrating our phenotypic results with protein interaction data, we constructed a genome-wide, functionally validated interaction network governing Notch signalling and asymmetric cell division. We used clustering algorithms to identify nuclear import pathways and the COP9 signallosome as Notch regulators. Our results show that complex developmental processes can be analysed on a genome-wide level and provide a unique resource for functional annotation of the Drosophila genome.
Screen detailsStable Id:
GR00144-A-4
Screen title:
Notch pathway regulation (4)
Assay:
External sensory organ morphology and viability
Method:
Visual inspection
Scope:
Genome-wide
Screen type:
in vivo
Species:
Drosophila melanogaster
Biosource:
Tissue
Biomodel:
pnr-GAL4
Library:
VDRC, np
Reagent type:
UAS-IR construct
Score type:
Phenotype strength
Cutoff:
np
Notes:
|
| Lipid storage | FBgn0052704
| | | -1.91 |
Lipid understorage
| 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:
|
| Dpp pathway regulation |
| Ir8a | | weak |
Decreased Flag-Mad nuclear accumulation
| no |
ReferenceMsk is required for nuclear import of TGF-{beta}/BMP-activated Smads. Xu et al.,
2007
Nuclear translocation of Smad proteins is a critical step in signal transduction of transforming growth factor beta (TGF-beta) and bone morphogenetic proteins (BMPs). Using nuclear accumulation of the Drosophila Smad Mothers against Decapentaplegic (Mad) as the readout, we carried out a whole-genome RNAi screening in Drosophila cells. The screen identified moleskin (msk) as important for the nuclear import of phosphorylated Mad. Genetic evidence in the developing eye imaginal discs also demonstrates the critical functions of msk in regulating phospho-Mad. Moreover, knockdown of importin 7 and 8 (Imp7 and 8), the mammalian orthologues of Msk, markedly impaired nuclear accumulation of Smad1 in response to BMP2 and of Smad2/3 in response to TGF-beta. Biochemical studies further suggest that Smads are novel nuclear import substrates of Imp7 and 8. We have thus identified new evolutionarily conserved proteins that are important in the signal transduction of TGF-beta and BMP into the nucleus.
Screen detailsStable Id:
GR00014-A
Screen title:
Dpp pathway regulation
Assay:
Flag-Mad protein expression and subcellular location
Method:
Fluorescence
Scope:
Genome-wide
Screen type:
Cell-based
Species:
Drosophila melanogaster
Biosource:
Cell line
Biomodel:
S2R+
Library:
rp, rp
Reagent type:
dsRNA
Score type:
Visual inspection
Cutoff:
np
Notes:
|
