The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans

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The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans. / Gonzalez, D A; Jia, T; Pinzón, J H; Acevedo, S F; Ojelade, S A; Xu, B; Tay, N; Desrivières, S; Hernandez, J L; Banaschewski, T; Büchel, C; Bokde, A L W; Conrod, P J; Flor, H; Frouin, V; Gallinat, J; Garavan, H; Gowland, P A; Heinz, A; Ittermann, B; Lathrop, M; Martinot, J-L; Paus, T; Smolka, M N; Rodan, A R; Schumann, G; Rothenfluh, A; IMAGEN Consortium.

In: MOL PSYCHIATR, Vol. 23, No. 3, 03.2018, p. 621-628.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Gonzalez, DA, Jia, T, Pinzón, JH, Acevedo, SF, Ojelade, SA, Xu, B, Tay, N, Desrivières, S, Hernandez, JL, Banaschewski, T, Büchel, C, Bokde, ALW, Conrod, PJ, Flor, H, Frouin, V, Gallinat, J, Garavan, H, Gowland, PA, Heinz, A, Ittermann, B, Lathrop, M, Martinot, J-L, Paus, T, Smolka, MN, Rodan, AR, Schumann, G, Rothenfluh, A & IMAGEN Consortium 2018, 'The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans', MOL PSYCHIATR, vol. 23, no. 3, pp. 621-628. https://doi.org/10.1038/mp.2017.112

APA

Gonzalez, D. A., Jia, T., Pinzón, J. H., Acevedo, S. F., Ojelade, S. A., Xu, B., Tay, N., Desrivières, S., Hernandez, J. L., Banaschewski, T., Büchel, C., Bokde, A. L. W., Conrod, P. J., Flor, H., Frouin, V., Gallinat, J., Garavan, H., Gowland, P. A., Heinz, A., ... IMAGEN Consortium (2018). The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans. MOL PSYCHIATR, 23(3), 621-628. https://doi.org/10.1038/mp.2017.112

Vancouver

Bibtex

@article{e8be1ee9eedf4899aaa92a9c20dc574a,
title = "The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans",
abstract = "Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors.",
keywords = "Journal Article",
author = "Gonzalez, {D A} and T Jia and Pinz{\'o}n, {J H} and Acevedo, {S F} and Ojelade, {S A} and B Xu and N Tay and S Desrivi{\`e}res and Hernandez, {J L} and T Banaschewski and C B{\"u}chel and Bokde, {A L W} and Conrod, {P J} and H Flor and V Frouin and J Gallinat and H Garavan and Gowland, {P A} and A Heinz and B Ittermann and M Lathrop and J-L Martinot and T Paus and Smolka, {M N} and Rodan, {A R} and G Schumann and A Rothenfluh and {IMAGEN Consortium}",
year = "2018",
month = mar,
doi = "10.1038/mp.2017.112",
language = "English",
volume = "23",
pages = "621--628",
journal = "MOL PSYCHIATR",
issn = "1359-4184",
publisher = "NATURE PUBLISHING GROUP",
number = "3",

}

RIS

TY - JOUR

T1 - The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans

AU - Gonzalez, D A

AU - Jia, T

AU - Pinzón, J H

AU - Acevedo, S F

AU - Ojelade, S A

AU - Xu, B

AU - Tay, N

AU - Desrivières, S

AU - Hernandez, J L

AU - Banaschewski, T

AU - Büchel, C

AU - Bokde, A L W

AU - Conrod, P J

AU - Flor, H

AU - Frouin, V

AU - Gallinat, J

AU - Garavan, H

AU - Gowland, P A

AU - Heinz, A

AU - Ittermann, B

AU - Lathrop, M

AU - Martinot, J-L

AU - Paus, T

AU - Smolka, M N

AU - Rodan, A R

AU - Schumann, G

AU - Rothenfluh, A

AU - IMAGEN Consortium

PY - 2018/3

Y1 - 2018/3

N2 - Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors.

AB - Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors.

KW - Journal Article

U2 - 10.1038/mp.2017.112

DO - 10.1038/mp.2017.112

M3 - SCORING: Journal article

C2 - 28607459

VL - 23

SP - 621

EP - 628

JO - MOL PSYCHIATR

JF - MOL PSYCHIATR

SN - 1359-4184

IS - 3

ER -