mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors.
mTORC1-dependent translation of collapsin response mediator protein-2 drives neuroadaptations underlying excessive alcohol-drinking behaviors.
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DOI：
10.1038/mp.2016.12
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发表时间：
2017-01
影响因子：
11
通讯作者：
Ron, D.
中科院分区：
文献类型：
--
作者：
Liu, F.;Laguesse, S.;Legastelois, R.;Morisot, N.;Ben Hamida, S.;Ron, D.
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.
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影响因子：
4.7
作者：
Gibb SL;Hamida SB;Lanfranco MF;Ron D
通讯作者：
Ron D
DOI：
10.1073/pnas.1308198110
发表时间：
2013-09-03
影响因子：
11.1
作者：
DePoy, Lauren;Daut, Rachel;Holmes, Andrew
通讯作者：
Holmes, Andrew
影响因子：
2.3
作者：
Camicella, Sebastien;Amamoto, Ryoji;Ron, Dorit
通讯作者：
Ron, Dorit
影响因子：
16.2
作者：
Hell JW
通讯作者：
Hell JW
影响因子：
3.4
作者：
Camp MC;Feyder M;Ihne J;Palachick B;Hurd B;Karlsson RM;Noronha B;Chen YC;Coba MP;Grant SG;Holmes A
通讯作者：
Holmes A