Human Disease Model Report: alcohol, response to, actin-mediated

General Information

Name

alcohol, response to, actin-mediated

FlyBase ID

FBhh0000698

Disease Ontology Term

alcohol use disorder

Parent Disease

alcohol use disorder, susceptibility to (fly models overview)

OMIM

Overview

A number of the genes involved in behavioral alcohol responses in flies, affecting ethanol sensitivity and/or tolerance, appear to act via actin remodeling. These include aru, Arf51F, ics, and cher. See review by Park et al., 2017 (FBrf0235911) for additional genes in this category.

[updated Jan. 2018 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: alcohol use disorder, susceptibility to (fly models overview)

Symptoms and phenotype

Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).

(FlyBase Curators, 2013-)

The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)

(FlyBase Curators, 2013-)

Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).

(FlyBase Curators, 2013-)

Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]

(OMIM, 2013-)

Specific Disease Summary: alcohol, response to, actin-mediated

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

Disease synonyms

alcohol, response to, actin remodeling

AUD susceptibility, actin-mediated

AUD susceptibility, actin remodeling

Search term: alcohol use disorder

Related Diseases

Related human health report(s)

alcohol, response to, ARF6-related

alcohol, response to, EPS8-related

alcohol, response to, F-actin turnover-related

alcohol, response to, RhoGAP-related

alcohol, response to, RSU1-related

alcohol use disorder, susceptibility to (fly models overview)

Related Specific Diseases

OMIM phenotypic series

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (4)

Dmel\aru

Gene Snapshot

arouser (aru) encodes an SH3 adaptor protein that interacts with Egfr and PI3K pathways. Its roles include regulation of synapse number, memory formation and ethanol sedation sensitivity. [Date last reviewed: 2019-03-07]

Molecular function (GO)

actin binding

Cellular component (GO)

Gene Groups / Pathways

EPS8

Comments on ortholog(s)

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\Arf6

Gene Snapshot

ADP ribosylation factor 6 (Arf6) belongs to the Arf family, which are members of the Ras superfamily of small GTPases. Arf proteins are involved in the regulation of vesicular trafficking mediating processes such as cargo-sorting, vesicle assembly and membrane fusion. Arf proteins regulate cell shape changes and cell movements in multiple organs. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\ics

Gene Snapshot

icarus (ics) encodes RSU1 (Ras suppressor 1), an adapter protein that participates in integrin-dependent processes by interacting with the integrin effector protein encoded by stck. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\cher

Gene Snapshot

cheerio (cher) encodes a dimeric F-actin crosslinking protein of the filamin protein family. It functions to organize the F-actin cytoskeleton in multiple contexts including ovarian germline ring canals, migrating somatic cells, and neuronal growth cones. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (30 groups)

aru

protein-protein

Interacting group

Assay

References

aru - Atg8a

anti bait coimmunoprecipitation, western blot, pull down, autoradiography

(Jacomin et al., 2021)

aru - Bsg

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Brent and Rajan, 2020)

aru - Slik

experimental knowledge based

(Guruharsha et al., 2011)

Arf6

protein-protein

Interacting group

Assay

References

Arf6 - Arfip

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Chang et al., 2013, Peru Y Colón de Portugal et al., 2012)

Arf6 - hh

anti bait coimmunoprecipitation, western blot

(Chabu et al., 2017)

Arf6 - Iqsec

enzymatic study, autoradiography

(Chen et al., 2003)

Arf6 - pav

pull down, western blot, two hybrid

(Dyer et al., 2007)

ics

protein-protein

Interacting group

Assay

References

ics - Ilk

anti tag coimmunoprecipitation, western blot

(Kadrmas et al., 2004)

ics - Rac1

anti tag coimmunoprecipitation, anti tag western blot

(Ojelade et al., 2015)

ics - stck

anti tag coimmunoprecipitation, peptide massfingerprinting, pull down, western blot, two hybrid

(Pronovost et al., 2013, Yoshigi et al., 2013, Elias et al., 2012, Kadrmas et al., 2004)

cher

protein-protein

Interacting group

Assay

References

cher - 14-3-3ε

anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry

(Külshammer et al., 2022)

cher - Actin

phenotype-based detection assay, fluorescence microscopy, inferred by author

(Green et al., 2018)

cher - bbg

anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry

(Külshammer et al., 2022)

cher - CG44250

two hybrid

(Hu et al., 2017.6.13)

cher - dos

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

cher - hts

proximity-dependent biotin identification, Identification by mass spectrometry, proximity ligation assay, fluorescence microscopy

(Mannix et al., 2019)

cher - InR

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

cher - kel

proximity-dependent biotin identification, Identification by mass spectrometry, western blot

(Mannix et al., 2019)

cher - l(2)efl

anti bait coimmunoprecipitation, anti tag western blot, peptide massfingerprinting

(Wójtowicz et al., 2015)

cher - Nuak

two hybrid

(Brooks et al., 2020)

cher - Pak

proximity ligation assay, fluorescence microscopy

(Lee and Schwarz, 2016)

cher - pll

two hybrid

(Edwards et al., 1997)

cher - Rab11

pull down, peptide massfingerprinting

(Ramel et al., 2013)

cher - Sema1a

anti bait coimmunoprecipitation, anti tag western blot, two hybrid

(Jeong et al., 2017)

cher - sls

pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot

(González-Morales et al., 2017)

cher - Ten-m

two hybrid, pull down, autoradiography

(Zheng et al., 2011)

cher - tub

two hybrid

(Edwards et al., 1997)

cher - Vinc

phenotype-based detection assay, fluorescence microscopy, inferred by author

(Green et al., 2018)

cher - wash

phenotype-based detection assay, fluorescence microscopy, inferred by author

(Green et al., 2018)

cher - zip

anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry

(Külshammer et al., 2022, Külshammer and Uhlirova, 2013)

Alleles Reported to Model Human Disease (Disease Ontology) (31 alleles)

aru

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

aru^d08896

model of alcohol use disorder

CEA

(Eddison et al., 2011)

aru^8.128

model of alcohol use disorder

CEA

(Eddison et al., 2011)

aru^RNAi.UAS

model of alcohol use disorder

CEA

(Eddison et al., 2011)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

aru^8.128

ameliorates alcohol use disorder

modeled by hppy^17-51

(Eddison et al., 2011)

model of alcohol use disorder

is ameliorated by Akt^EY10012

(Eddison et al., 2011)

Arf6

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

Arf6^EP2612

model of alcohol use disorder

CEA

(Gonzalez et al., 2018)

CEA with Arf6^NP5226

(Gonzalez et al., 2018)

Arf6^KK108126

model of candidiasis

CEA

(Glittenberg et al., 2022)

Arf6^NP5226

model of alcohol use disorder

CEA with Arf6^EP2612

(Gonzalez et al., 2018)

Modifiers Based on Experimental Evidence ( 0 )

Allele

Disease

Interaction

References

ics

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

ics^G4

model of alcohol dependence

CEA

(Ojelade et al., 2015)

ics^RNAi.UAS.WIZ

model of alcohol dependence

CEA

(Ojelade et al., 2015)

Modifiers Based on Experimental Evidence ( 0 )

Allele

Disease

Interaction

References

cher

Models Based on Experimental Evidence ( 22 )

Allele

Disease

Evidence

References

cher¹

model of myopathy

CEA with Act88F⁶

(González-Morales et al., 2017)

cher^EPSΔ5

model of myopathy

CEA

(González-Morales et al., 2017)

CEA with sls^j1D7

(González-Morales et al., 2017)

CEA with Act88F⁶

(González-Morales et al., 2017)

cher^Q1042X

model of myopathy

CEA

(González-Morales et al., 2017)

DOES NOT model myopathy

CEA with sls^j1D7

(González-Morales et al., 2017)

cher^sko

model of myopathy

CEA

(González-Morales et al., 2017)

CEA with sls^j1D7

(González-Morales et al., 2017)

DOES NOT model myopathy

CEA with Act88F⁶

(González-Morales et al., 2017)

cher^CPTI001403

model of myopathy

CEA with Act88F⁶

(González-Morales et al., 2017)

DOES NOT model myopathy

CEA with sls^ZCL2144

(González-Morales et al., 2017)

cher^KK107518

model of myopathy

CEA

(González-Morales et al., 2017)

CEA with cher^JF02077

(González-Morales et al., 2017)

cher^JF02077

model of myopathy

CEA

(González-Morales et al., 2017)

CEA with cher^KK107518

(González-Morales et al., 2017)

model of distal myopathy 4

CEA

(Ader et al., 2022)

model of myofibrillar myopathy 5

CEA

(Ader et al., 2022)

cher^I1849T.STOP

model of myopathy

CEA

(Ader et al., 2022)

cher^V1865L.STOP

DOES NOT model myopathy

CEA

(Ader et al., 2022)

cher^G1789S.STOP

model of myopathy

CEA

(Ader et al., 2022)

cher^I1849T

DOES NOT model myopathy

CEA

(Ader et al., 2022)

cher^V1865L

DOES NOT model myopathy

CEA

(Ader et al., 2022)

cher^G1789S

DOES NOT model myopathy

CEA

(Ader et al., 2022)

cher^{closedMSR.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^ΔMSR.mGFP6

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg14-22.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg14-21.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg15-21.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg16-17.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg18-19.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^{ΔIg20-21.mGFP6}

model of myopathy

CEA

(Fisher et al., 2024)

cher^ΔIg22.mGFP6

model of myopathy

CEA

(Fisher et al., 2024)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

cher^EP3715

exacerbates tauopathy

modeled by Hsap\MAPT^V337M.UAS

(Shulman and Feany, 2003)

cher^JF02077

model of myopathy

is exacerbated by sls¹

(González-Morales et al., 2017)

is exacerbated by sls^j1D7

(González-Morales et al., 2017)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

aru^GD11269

P{GD11269}

w¹¹¹⁸; P{GD11269}v26482

y¹ v¹; P{TRiP.HMJ21663}attP40/CyO

aru^HMS02966

P{TRiP.HMS02966}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS02966}attP2/TM3, Sb¹

ics^GD14099

P{GD14099}

w¹¹¹⁸; P{GD14099}v42188

w¹¹¹⁸; P{GD13822}v24224

y¹ v¹; P{TRiP.JF02549}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.GLC01795}attP2

y¹ v¹; P{TRiP.JF02077}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01501}attP2/TM3, Sb¹

cher^NIG.3937R

P{NIG.3937R}

P{NIG.3937R}2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

aru^d08896

P-element activity

w¹¹¹⁸; P{XP}aru^d08896

aru^8.128

P-element activity

ics^BG02577

loss of function allele

P-element activity

w¹¹¹⁸; P{GT1}ics^BG02577

ics^G4

Arf6^EP2612

amorphic allele - genetic evidence

P-element activity

w¹¹¹⁸; P{EP}Arf6^EP2612/CyO

Arf6^KO2

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^KO3

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^KO16

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^KO25

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^KO27

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^NP5226

amorphic allele - genetic evidence

y^* w^*; P{GawB}Arf6^NP5226 / CyO, P{UAS-lacZ.UW14}UW14

Arf6^GX16w-

amorphic allele - molecular evidence

gene targeting by homologous recombination

w^*; TI{TI}Arf6^GX16w-/CyO, P{Wee-P.ph0}Bacc^Wee-P20

Arf6^KO

amorphic allele - molecular evidence

ends-out gene targeting

P-element activity

CRISPR/Cas9

CRISPR/Cas9

CRISPR/Cas9

piggyBac activity

piggyBac activity

piggyBac activity

cher^{closedMSR.mGFP6}

phiC31 integrase

cher^ΔMSR.mGFP6

phiC31 integrase

cher^{ΔIg14-22.mGFP6}

cher^{ΔIg14-21.mGFP6}

cher^{ΔIg15-21.mGFP6}

cher^{ΔIg16-17.mGFP6}

cher^{ΔIg18-19.mGFP6}

cher^{ΔIg20-21.mGFP6}

cher^ΔIg22.mGFP6

cher^sko

ethyl methanesulfonate

cher¹

amorphic allele - genetic evidence

cher^EPSΔ5

Delta2-3 transposase

cher^EPSΔ12.1

amorphic allele - molecular evidence

Delta2-3 transposase

cher^Q1042X

cher^CPTI001403

piggyBac activity

w¹¹¹⁸; PBac{681.P.FSVS-1}cher^CPTI001403

References (5)

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