Rsu1 regulates ethanol consumption in Drosophila and humans

Shamsideen A. Ojelade, Tianye Jia, Aylin R. Rodan, Tao Chenyang, Julie L. Kadrmas, Anna Cattrell, Barbara Ruggeri, Pimphen Charoen, Hervé Lemaitre, Tobias Banaschewski, Christian Büchel, Arun L W Bokde, Fabiana Carvalho, Patricia J. Conrod, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Penny A. Gowland, Andreas Heinz & 15 others Bernd Ittermann, Mark Lathrop, Steven Lubbe, Jean Luc Martinot, Tomás Pausu, Michael N. Smolka, Rainer Spanagel, Paul F. O'Reilly, Jaana Laitinen, Juha M. Veijola, Jianfeng Feng, Sylvane Desrivières, Marjo Riitta Jarvelin, Gunter Schumann, Adrian Rothenfluh

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)E4085-E4093
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number30
DOIs
StatePublished - Jul 28 2015

Fingerprint

Drosophila
Ethanol
Diptera
Integrins
rac1 GTP-Binding Protein
Mushroom Bodies
GTP Phosphohydrolases
Brain
Cell Adhesion Molecules
Actin Cytoskeleton
Reward
Nervous System
Alcoholism
Actins
Phenotype
Neurons

Keywords

  • Actin
  • Addiction
  • Alcohol
  • Genetics

ASJC Scopus subject areas

  • General

Cite this

Rsu1 regulates ethanol consumption in Drosophila and humans. / 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; Pausu, Tomás; Smolka, Michael N.; Spanagel, Rainer; O'Reilly, Paul F.; Laitinen, Jaana; Veijola, Juha M.; Feng, Jianfeng; Desrivières, Sylvane; Jarvelin, Marjo Riitta; Schumann, Gunter; Rothenfluh, Adrian.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 30, 28.07.2015, p. E4085-E4093.

Research output: Contribution to journalArticle

Ojelade, SA, Jia, T, Rodan, AR, Chenyang, T, Kadrmas, JL, Cattrell, A, Ruggeri, B, Charoen, P, Lemaitre, H, Banaschewski, T, Büchel, C, Bokde, ALW, Carvalho, F, Conrod, PJ, Flor, H, Frouin, V, Gallinat, J, Garavan, H, Gowland, PA, Heinz, A, Ittermann, B, Lathrop, M, Lubbe, S, Martinot, JL, Pausu, T, Smolka, MN, Spanagel, R, O'Reilly, PF, Laitinen, J, Veijola, JM, Feng, J, Desrivières, S, Jarvelin, MR, Schumann, G & Rothenfluh, A 2015, 'Rsu1 regulates ethanol consumption in Drosophila and humans', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 30, pp. E4085-E4093. https://doi.org/10.1073/pnas.1417222112
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 ; Pausu, Tomás ; Smolka, Michael N. ; Spanagel, Rainer ; O'Reilly, Paul F. ; Laitinen, Jaana ; Veijola, Juha M. ; Feng, Jianfeng ; Desrivières, Sylvane ; Jarvelin, Marjo Riitta ; Schumann, Gunter ; Rothenfluh, Adrian. / Rsu1 regulates ethanol consumption in Drosophila and humans. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 30. pp. E4085-E4093.
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AU - Ojelade, Shamsideen A.

AU - Jia, Tianye

AU - Rodan, Aylin R.

AU - Chenyang, Tao

AU - Kadrmas, Julie L.

AU - Cattrell, Anna

AU - Ruggeri, Barbara

AU - Charoen, Pimphen

AU - Lemaitre, Hervé

AU - Banaschewski, Tobias

AU - Büchel, Christian

AU - Bokde, Arun L W

AU - Carvalho, Fabiana

AU - Conrod, Patricia J.

AU - Flor, Herta

AU - Frouin, Vincent

AU - Gallinat, Jürgen

AU - Garavan, Hugh

AU - Gowland, Penny A.

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Lathrop, Mark

AU - Lubbe, Steven

AU - Martinot, Jean Luc

AU - Pausu, Tomás

AU - Smolka, Michael N.

AU - Spanagel, Rainer

AU - O'Reilly, Paul F.

AU - Laitinen, Jaana

AU - Veijola, Juha M.

AU - Feng, Jianfeng

AU - Desrivières, Sylvane

AU - Jarvelin, Marjo Riitta

AU - Schumann, Gunter

AU - Rothenfluh, Adrian

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