Details

Autor(en) / Beteiligte

• 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
• Veijolaa, Juha M.
• Feng, Jianfeng
• Desrivières, Sylvane
• Jarvelin, Marjo-Riitta
• Schumann, Gunter
• Rothenfluh, Adrian

Titel

Rsu1 regulates ethanol consumption inDrosophilaand humans

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-07, Vol.112 (30), p.E4085-E4093

Ort / Verlag

National Academy of Sciences

Erscheinungsjahr

2015

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.Drosophilalacking 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 inRSU1are 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.