Rsu1 regulates ethanol consumption in
Drosophila
and humans
Authors: Ojelade Shamsideen A. , Jia Tianye , Rodan Aylin R. , Chenyang Tao , Kadrmas Julie L. , Cattrell Anna , Ruggeri Barbara , Charoen Pimphen , Lemaitre Hervé , Banaschewski Tobias , Büchel Christian , Bokde Arun L. W. , Carvalho Fabiana , Conrod Patricia J. , Flor Herta , Frouin Vincent , Gallinat Jürgen , Garavan Hugh , Gowland Penny A. , Heinz Andreas , Ittermann Bernd , Lathrop Mark , Lubbe Steven , Martinot Jean-Luc , Paus Tomás , Smolka Michael N. , Spanagel Rainer , O’Reilly Paul F. , Laitinen Jaana , Veijola Juha M. , Feng Jianfeng , Desrivières Sylvane , Jarvelin Marjo-Riitta ,   The IMAGEN Consortium, Schumann Gunter , Rothenfluh Adrian , Albrecht Lisa ,   Charite, Arroyo Mercedes ,   Cambridge University, Artiges Eric ,   INSERM, Aydin Semiha ,   Physikalisch-Technische Bundesanstalt, Bach Christine ,   Central Institute of Mental Health, Banaschewski Tobias ,   Central Institute of Mental Health, Barbot Alexis ,   Commissariat à l'Energie Atomique, Barker Gareth ,   King’s College, Bokde Arun ,   Trinity College Dublin, Bricaud Zuleima ,   INSERM, Bromberg Uli ,   University of Hamburg, Bruehl Ruediger ,   Physikalisch-Technische Bundesanstalt, Büchel Christian ,   University of Hamburg, Cattrell Anna ,   King’s College, Conrod Patricia ,   King’s College, Czech Katharina ,   Charite, Dalley Jeffrey ,   Cambridge University, Desrivieres Sylvane ,   King’s College, Fadai Tahmine ,   University of Hamburg, Flor Herta ,   Central Institute of Mental Health, Frouin Vincent ,   Commissariat à l'Energie Atomique, Gallinat Jürgen ,   Charite, Garavan Hugh ,   Trinity College Dublin, Briand Fanny Gollier ,   INSERM, Gowland Penny ,   University of Nottingham, Heinrichs Bert ,   Deutsches Referenzzentrum für Ethik, Heinz Andreas ,   Charite, Hübner Thomas ,   Technische Universität Dresden, Ihlenfeld Albrecht ,   Physikalisch-Technische Bundesanstalt, Ing Alex ,   King's College, Ittermann Bernd ,   Physikalisch-Technische Bundesanstalt, Jia Tianye ,   King’s College, Jones Jennifer ,   Trinity College Dublin, Kennedy Eleanor ,   King's College, Lanzerath Dirk ,   Deutsches Referenzzentrum für Ethik, Lathrop Mark ,   McGill University, Lawrence Claire ,   University of Nottingham, Lemaitre Hervé ,   INSERM, Lüdemann Katharina ,   Charite, Lubbe Steven ,   King’s College, Macare Christine ,   King's College, Mann Karl ,   Central Institute of Mental Health, Mar Adam ,   Cambridge University, Martinot Jean-Luc ,   INSERM, Mennigen Eva ,   Technische Universität Dresden, Mesquita de Carvahlo Fabiana ,   King’s College, Müller Kathrin ,   Technische Universität Dresden, Nees Frauke ,   Central Institute of Mental Health, Nymberg Charlotte ,   King’s College, Paillere Marie-Laure ,   INSERM, Paus Tomas ,   University of Toronto, Pausova Zdenka ,   University of Toronto, Poline Jean-Baptiste ,   Commissariat à l'Energie Atomique, Poustka Luise ,   Central Institute of Mental Health, Quinlan Erin ,   King's College, Reuter Jan ,   Charite, Ripke Stephan ,   Technische Universität Dresden, Robbins Trevor ,   Cambridge University, Robert Gabriel ,   King's College, Rodehacke Sarah ,   Technische Universität Dresden, Ruggeri Barbara ,   King’s College, Schmidt Dirk ,   Technische Universität Dresden, Schneider Sophia ,   University of Hamburg, Schubert Florian ,   Physikalisch-Technische Bundesanstalt, Smolka Michael ,   Technische Universität Dresden, Sommer Wolfgang ,   Central Institute of Mental Health, Spanagel Rainer ,   Central Institute of Mental Health,   Claudia Speiser. GABO:milliarium mbH & Co. KG, Spranger Tade ,   Deutsches Referenzzentrum für Ethik, Stedman Alicia ,   University of Nottingham, Stephens Dai ,   University of Sussex, Strache Nicole ,   Charite, Ströhle Andreas ,   Charite, Struve Maren ,   Central Institute of Mental Health, Subramaniam Naresh ,   Cambridge University, Tahmasebi Amir ,   University of Toronto, Theobald David ,   Cambridge University, Vetter Nora ,   TU Dresden, Vulser Helene ,   INSERM, Walaszek Bernadeta ,   Physikalisch-Technische Bundesanstalt, Whelan Robert ,   Trinity College Dublin, Williams Steve ,   King’s College, Xu Bing ,   King's College, Yacubian Juliana ,   University of Hamburg, Ziesch Veronika ,   Technische Universität Dresden
Published: July 2015

Significance

Genetic factors play a major role in the development of human addiction. Identifying these genes and understanding their molecular mechanisms are necessary first steps in the development of targeted therapeutic intervention. Here, we have isolated the gene encoding Ras suppressor 1 (Rsu1) in an unbiased genetic screen for altered ethanol responses in the vinegar fly,
Drosophila melanogaster
. Our behavioral, genetic, and biochemical experiments show that Rsu1 links signaling from the integrin cell adhesion molecule to the small GTPase Rac1 in adult neurons to regulate actin dynamics and alcohol consumption preference. We also show that variants in human
RSU1
associate with altered drinking and brain activation during a reward prediction task, thereby validating the predictive power of our approach.