Article (Scientific journals)
MTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors
Liu, F.; Laguesse, Sophie; Legastelois, R. et al.
2017In Molecular Psychiatry, 22 (1), p. 89-101
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Keywords :
Article; CRMP 2 gene; RNA translation; C57BL mouse; Long Evans rat; Acetamides; Alcohol Drinking; Animals; Dendrites; Ethanol; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Intercellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Microtubules; Multiprotein Complexes; Nerve Tissue Proteins; Nucleus Accumbens; Phosphorylation; Protein Biosynthesis; Rats; Rats, Long-Evans; Signal Transduction; TOR Serine-Threonine Kinases
Abstract :
[en] Mammalian target of rapamycin complex 1 (mTORC1) has an essential role in dendritic mRNA translation and participates in mechanisms underlying alcohol-drinking and reconsolidation of alcohol-related memories. Here, we report that excessive alcohol consumption increases the translation of downstream targets of mTORC1, including collapsin response mediator protein-2 (CRMP-2), in the nucleus accumbens (NAc) of rodents. We show that alcohol-mediated induction of CRMP-2 translation is mTORC1-dependent, leading to increased CRMP-2 protein levels. Furthermore, we demonstrate that alcohol intake also blocks glycogen synthase kinase-3β (GSK-3β)-phosphorylation of CRMP-2, which results in elevated binding of CRMP-2 to microtubules and a concomitant increase in microtubule content. Finally, we show that systemic administration of the CRMP-2 inhibitor lacosamide, or knockdown of CRMP-2 in the NAc decreases excessive alcohol intake. These results suggest that CRMP-2 in the NAc is a convergent point that receives inputs from two signaling pathways, mTORC1 and GSK-3β, that in turn drives excessive alcohol-drinking behaviors. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Research center :
UCSF - Neurology Unit - Ron lab
Disciplines :
Neurology
Author, co-author :
Liu, F.;  Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, United States, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
Laguesse, Sophie  ;  Université de Liège - ULiège > Giga - Neurosciences
Legastelois, R.;  Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, United States, INSERM ERi24, Université de Picardie, Amiens, France
Morisot, N.;  Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, United States
Ben Hamida, S.;  Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, United States, McGill University, Montreal, Canada
Ron, D.;  Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA, United States
Language :
English
Title :
MTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors
Publication date :
2017
Journal title :
Molecular Psychiatry
ISSN :
1359-4184
eISSN :
1476-5578
Publisher :
Nature Publishing Group
Volume :
22
Issue :
1
Pages :
89-101
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 04 February 2019

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