Rsu1 regulates ethanol consumption in Drosophila and humans

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Shamsideen A. Ojelade - , University of Texas Southwestern Medical Center (Autor:in)
  • Tianye Jia - , King's College London (KCL) (Autor:in)
  • Aylin R. Rodan - , University of Texas Southwestern Medical Center (Autor:in)
  • Tao Chenyang - , Fudan University, University of Warwick (Autor:in)
  • Julie L. Kadrmas - , University of Utah (Autor:in)
  • Anna Cattrell - , King's College London (KCL) (Autor:in)
  • Barbara Ruggeri - , King's College London (KCL) (Autor:in)
  • Pimphen Charoen - , Imperial College London, Mahidol University (Autor:in)
  • Hervé Lemaitre - , INSERM - Institut national de la santé et de la recherche médicale, Assistance publique – Hôpitaux de Paris (Autor:in)
  • Tobias Banaschewski - , Universität Heidelberg (Autor:in)
  • Christian Büchel - , Universität Hamburg (Autor:in)
  • Arun L.W. Bokde - , Trinity College Dublin (Autor:in)
  • Fabiana Carvalho - , King's College London (KCL) (Autor:in)
  • Patricia J. Conrod - , King's College London (KCL), University of Montreal (Autor:in)
  • Herta Flor - , Universität Heidelberg (Autor:in)
  • Vincent Frouin - , Commissariat à l’énergie atomique et aux énergies alternatives (CEA) (Autor:in)
  • Jürgen Gallinat - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Hugh Garavan - , Trinity College Dublin, University of Vermont (Autor:in)
  • Penny A. Gowland - , University of Nottingham (Autor:in)
  • Andreas Heinz - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Bernd Ittermann - , University of Nottingham (Autor:in)
  • Mark Lathrop - , Commissariat à l’énergie atomique et aux énergies alternatives (CEA) (Autor:in)
  • Steven Lubbe - , King's College London (KCL) (Autor:in)
  • Jean Luc Martinot - , INSERM - Institut national de la santé et de la recherche médicale, Assistance publique – Hôpitaux de Paris (Autor:in)
  • Tomás Pausu - , University of Nottingham, University of Toronto, Centre Universitaire de Sante McGill (Autor:in)
  • Michael N. Smolka - , Klinik und Poliklinik für Psychiatrie und Psychotherapie, Neuroimaging Center (Autor:in)
  • Rainer Spanagel - , Universität Heidelberg (Autor:in)
  • Paul F. O'Reilly - , King's College London (KCL) (Autor:in)
  • Jaana Laitinen - , Finnish Institute of Occupational Health (Autor:in)
  • Juha M. Veijola - , University of Oulu (Autor:in)
  • Jianfeng Feng - , Fudan University, University of Warwick (Autor:in)
  • Sylvane Desrivières - , King's College London (KCL) (Autor:in)
  • Marjo Riitta Jarvelin - , Imperial College London, University of Oulu, National Institute for Health and Welfare (Autor:in)
  • Gunter Schumann - , King's College London (KCL) (Autor:in)
  • Adrian Rothenfluh - , University of Texas Southwestern Medical Center (Autor:in)

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 tomodulate 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 rewardrelated phenotypes, including ethanol consumption, across phyla.

Details

OriginalspracheEnglisch
Seiten (von - bis)E4085-E4093
FachzeitschriftProceedings of the National Academy of Sciences of the United States of America
Jahrgang112
Ausgabenummer30
PublikationsstatusVeröffentlicht - 28 Juli 2015
Peer-Review-StatusJa

Externe IDs

PubMed 26170296
ORCID /0000-0001-5398-5569/work/161890791

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • Actin, Addiction, Alcohol, Genetics