ArticleProceedings of the National Academy of Sciences of the United States of America2015
Rsu1 regulates ethanol consumption in Drosophila and humans.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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50citing papers in PubMed, 2 pooled it
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- The IMAGEN study: a decade of imaging genetics in adolescents.Molecular psychiatry · 2020Pooled it
- New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.Nature human behaviour · 2019Pooled it
- High-throughput mechanomic screening reveals novel regulators of single-cell mechanics.Biophysical journal · 2026Article
- Alternative 3' Polyadenylation Responses to Acute Ethanol Exposure Differ Between Drosophila Populations.Research square · 2026Article
- Hippocampal Cofilin and CFL1 gene variants are linked to Alcohol Use Disorder phenotypes.Molecular psychiatry · 2026Article
- Bitter Sensing ProtectsThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- From Natural Behavior to Drug Screening: Invertebrates as Models to Study Mechanisms Associated with Alcohol Use Disorders.Current topics in behavioral neurosciences · 2025Review
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- Targeting the cytoskeleton as a therapeutic approach to substance use disorders.Pharmacological research · 2024Review
- Large analysis of genetic manipulations reveals an inverse correlation between initial alcohol resistance and rapid tolerance phenotypes.Genes, brain, and behavior · 2024Article
- Large genetic analysis of alcohol resistance and tolerance reveals an inverse correlation and suggests 'true' tolerance mutants.bioRxiv : the preprint server for biology · 2023Article
- Molecular fingerprints in the hippocampus of alcohol seeking during withdrawal.Research square · 2023Article
- Molecular fingerprints in the hippocampus of alcohol seeking during withdrawal.bioRxiv : the preprint server for biology · 2023Article
- The Stage-Based Model of Addiction-UsingInternational journal of molecular sciences · 2023Review
- Gene-environment interactions in birth defect etiology: Challenges and opportunities.Current topics in developmental biology · 2023Review
- Optimized assay for transposase-accessible chromatin by sequencing (ATAC-seq) library preparation from adult Drosophila melanogaster neurons.Scientific reports · 2022Article
- Translational relevance of forward genetic screens in animal models for the study of psychiatric disease.Neuroscience and biobehavioral reviews · 2022Review
- The Use ofBiomedicines · 2022Review
- Alcohol and the brain: from genes to circuits.Trends in neurosciences · 2021Review
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Authors and funding
36 authors at 20 institutions in 9 countries.
Shamsideen A OjeladeDepartment of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390; Program in Neuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390;
Tianye JiaInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom;
Aylin R RodanDepartment of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390;
Tao ChenyangCenter for Computational Systems Biology, Faculty of Mathematics, Fudan University, Shanghai 200433, China; Department of Computer Science, Warwick University, Coventry CV4 7AL, United Kingdom;
Julie L KadrmasDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112;
Anna CattrellInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom;
Barbara RuggeriInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom;
Pimphen CharoenDepartment of Epidemiology and Biostatistics, MRC Health Protection Agency Centre for Environment and Health, School of Public Health, Imperial College London W2 1PG, London, United Kingdom; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;
Hervé LemaitreINSERM, INSERM Commissariat à l'Energie Atomique (CEA) Unit 1000 Imaging and Psychiatry, University Paris Sud, 91401 Orsay, France; Assistance Publique Hôpitaux de Paris Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75013 Paris, France;
Tobias BanaschewskiCentral Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Heidelberg, Germany;
Christian BüchelDepartment for Systems Neuroscience, Universitätsklinikum Hamburg Eppendorf, D-20246 Hamburg, Germany;
Arun L W BokdeInstitute of Neuroscience, Trinity College, Dublin 2, Ireland;
Fabiana CarvalhoInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom;
Patricia J ConrodInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Department of Psychiatry, Université de Montreal, Centre Hospitalier Universitaire Ste Justine Hospital, Montreal, QC, Canada H3T 1C5;
Herta FlorCentral Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Heidelberg, Germany;
Vincent FrouinNeurospin, Commissariat à l'Energie Atomique, 91191 Gif-sur-Yvette, France;
Jürgen GallinatDepartment of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin, 10117 Berlin, Germany;
Hugh GaravanInstitute of Neuroscience, Trinity College, Dublin 2, Ireland; Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT 05405;
Penny A GowlandSir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
Andreas HeinzDepartment of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin, 10117 Berlin, Germany;
Bernd IttermannSir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
Mark LathropCEA, Centre National de Génotypage, 91057 Evry, France;
Steven LubbeInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom;
Jean-Luc MartinotINSERM, INSERM Commissariat à l'Energie Atomique (CEA) Unit 1000 Imaging and Psychiatry, University Paris Sud, 91401 Orsay, France; Assistance Publique Hôpitaux de Paris Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, 75013 Paris, France;
Tomás PausSchool of Psychology, University of Nottingham, Nottingham NG7 2RD, United Kingdom; Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada M6A 2E1; Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4;
Michael N SmolkaDepartment of Psychiatry and Psychotherapy, Technische Universität Dresden, 01187 Dresden, Germany; Neuroimaging Center, Department of Psychology, Technische Universität Dresden, 01062 Dresden, Germany;ORCID http://orcid.org/0000-0001-5398-5569
Rainer SpanagelCentral Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Heidelberg, Germany;
Paul F O'ReillyInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom;
Jaana LaitinenCentre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, FI-00250, Helsinki, Finland;
Juha M VeijolaDepartment of Psychiatry, University of Oulu and Oulu University Hospital, 90210, Oulu, Finland;
Jianfeng FengCenter for Computational Systems Biology, Faculty of Mathematics, Fudan University, Shanghai 200433, China; Department of Computer Science, Warwick University, Coventry CV4 7AL, United Kingdom; School of Life Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200433, China;
Sylvane DesrivièresInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom;
Marjo-Riitta JarvelinDepartment of Epidemiology and Biostatistics, MRC Health Protection Agency Centre for Environment and Health, School of Public Health, Imperial College London W2 1PG, London, United Kingdom; Institute of Health Sciences, University of Oulu, FI-90014, Oulu, Finland; Biocenter Oulu, University of Oulu, FI-90014, Oulu, Finland; Unit of Primary Care, Oulu University Hospital, FI-90220, Oulu, Finland; Department of Children and Young People and Families, National Institute for Health and Welfare, FI-90101, Oulu, Finland.
IMAGEN Consortium
Gunter SchumannInstitute of Psychiatry, King's College London, London SE5 8AF, United Kingdom; Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Centre, London SE5 8AF, United Kingdom; Gunter.Schumann@kcl.ac.uk Adrian.Rothenfluh@utsouthwestern.edu.
Adrian RothenfluhDepartment of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390; Program in Neuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390; Gunter.Schumann@kcl.ac.uk Adrian.Rothenfluh@utsouthwestern.edu.
King's College London · GBHeidelberg University · DEUniversity of Nottingham · GBCharité - Universitätsmedizin Berlin · DECommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRInserm · FRTechnische Universität Dresden · DEThe University of Texas Southwestern Medical Center · USUniversity of Vermont · USFudan University · CNMontreal Neurological Institute and Hospital · CAOulu University Hospital · FITrinity College Dublin · IEUniversität Hamburg · DEUniversité Paris-Sud · FRUniversity of Utah · USFinnish Institute for Health and Welfare · FIFinnish Institute of Occupational Health · FIMahidol University · THUniversity Medical Center Hamburg-Eppendorf · DE
Funding
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1MBasic Science Training Program in Drug Abuse ResearchT32DA007290 · NIDA · YALE UNIVERSITY · PI SELF, DAVID W · 1992 to 2017
$6.7MControl of Alcohol Responses by Actin-Regulating GenesR01AA019526 · NIAAA · UT SOUTHWESTERN MEDICAL CENTER · PI ROTHENFLUH, ADRIAN · 2010 to 2025
$5.4MGenetics of cardiovascular risk factors in large founder population birth controlR01HL087679 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HIRSCHHORN, JOEL N · 2007 to 2009
$4.0MGenetic Influences on ADHD in a Finnish Birth CohortR01MH063706 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMALLEY, SUSAN L · 2001 to 2005
$3.3MWhole Genome Assoc. Analysis Strategies for Multi. PhenotypesRL1MH083268 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B. · 2007 to 2011
$2.1MMechanisms for regulation of cell adhesion and migrationR01GM084103 · NIGMS · UNIVERSITY OF UTAH · PI KADRMAS, JULIE L · 2009 to 2013
$1.4MWNK & SPAK/OSR1 regulation of SLC12 cotransporters in DrosophilaK08DK091316 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI RODAN, AYLIN RACHEL · 2011 to 2015
$727kRole of icarus in ethanol-induced behaviorsF31AA021340 · NIAAA · UT SOUTHWESTERN MEDICAL CENTER · PI OJELADE, SHAMSIDEEN A · 2012 to 2013
$59kMedical Research Council 93558Medical Research Council G0500539Medical Research Council G0600705Medical Research Council G0901858Medical Research Council G1002319Medical Research Council MC_UP_0801/1NHLBI NIH HHS 5R01HL087679-02NHLBI NIH HHS R01 HL087679NIAAA NIH HHS F31 AA021340NIAAA NIH HHS F31AA021340NIAAA NIH HHS R01 AA019526NIAAA NIH HHS R01AA019526NIBIB NIH HHS U54 EB020403NIDA NIH HHS DA007290NIDA NIH HHS T32 DA007290NIDDK NIH HHS K08 DK091316NIDDK NIH HHS K08DK091316NIGMS NIH HHS R01 GM084103NIGMS NIH HHS R01GM084103NIMH NIH HHS 1RL1MH083268-01NIMH NIH HHS R01 MH063706NIMH NIH HHS R01MH63706:02NIMH NIH HHS RL1 MH083268
Abstract
Alcohol abuse is highly prevalent, but little is understood about the molecular causes. Here, we report that Ras suppressor 1 (Rsu1) affects ethanol consumption in flies and humans. Drosophila lacking Rsu1 show reduced sensitivity to ethanol-induced sedation. We show that Rsu1 is required in the adult nervous system for normal sensitivity and that it acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase to regulate the actin cytoskeleton. In an ethanol preference assay, global loss of Rsu1 causes high naïve preference. In contrast, flies lacking Rsu1 only in the mushroom bodies of the brain show normal naïve preference but then fail to acquire ethanol preference like normal flies. Rsu1 is, thus, required in distinct neurons to modulate naïve and acquired ethanol preference. In humans, we find that polymorphisms in RSU1 are associated with brain activation in the ventral striatum during reward anticipation in adolescents and alcohol consumption in both adolescents and adults. Together, these data suggest a conserved role for integrin/Rsu1/Rac1/actin signaling in modulating reward-related phenotypes, including ethanol consumption, across phyla.
Indexed as
ActinsAdolescentAdultAlcohol DrinkingAnimalsBrainCell Adhesion MoleculesChildCohort StudiesCytoskeletonDrosophila ProteinsEthanolFemaleGenes, DominantGTP PhosphohydrolasesHumansActinsCell Adhesion MoleculesDrosophila ProteinsEthanolGTP Phosphohydrolasesics protein, DrosophilaIntegrinsRSU1 protein, humanTranscription Factorsactinaddictionalcoholgenetics
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