Ethanol-induced increase in Fyn kinase activity in the dorsomedial striatum is associated with subcellular redistribution of protein tyrosine phosphatase α.
Ethanol-induced increase in Fyn kinase activity in the dorsomedial striatum is associated with subcellular redistribution of protein tyrosine phosphatase α.
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DOI：
10.1111/j.1471-4159.2011.07485.x
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发表时间：
2011-11
影响因子：
4.7
通讯作者：
Ron D
中科院分区：
文献类型：
--
作者：
Gibb SL;Hamida SB;Lanfranco MF;Ron D
啮齿动物体内暴露于乙醇会导致背内侧纹状体 (DMS) 中 Fyn 激酶活性长期持续增加。在这里，我们着手确定一种分子机制，该机制有助于增强 Fyn 响应 DMS 中乙醇的活性。蛋白酪氨酸磷酸酶 α (PTPα) 正向调节 Fyn 的活性，我们发现重复全身给药或大量饮酒会导致 PTPα 在 DMS 中的突触定位增加，DMS 与 Fyn 所在的位置相同。我们还证明，过量饮酒会导致 Fyn 活性增加，并导致 Fyn 和 PTPα 在 DMS 脂筏中共定位。最后，我们发现突触部分中酪氨酸磷酸化（因此具有活性）PTPα 的水平随着大鼠偶然或非偶然接触乙醇而增加。总之，我们的结果表明，DMS 中的 PTPα 重新分配到 Fyn 所在的区室中，是一种潜在机制，通过该机制，乙醇暴露后激酶的活性增加。这种神经适应可能是导致过度乙醇消耗的机制的一部分。
In vivo exposure of rodents to ethanol leads to a long-lasting increase in Fyn kinase activity in the dorsomedial striatum (DMS). Here we set out to identify a molecular mechanism that contributes to the enhancement of Fyn activity in response to ethanol in the DMS. Protein tyrosine phosphatase α (PTPα) positively regulates the activity of Fyn, and we found that repeated systemic administration or binge drinking of ethanol results in an increase in the synaptic localization of PTPα in the DMS, the same site where Fyn resides. We also demonstrate that binge drinking of ethanol leads an increase in Fyn activity and to the co-localization of Fyn and PTPα in lipid rafts in the DMS. Finally, we show that the level of tyrosine phosphorylated (and thus active) PTPα in the synaptic fractions is increased in response to contingent or non-contingent exposure of rats to ethanol. Together, our results suggest that the redistribution of PTPα in the DMS into compartments where Fyn resides is a potential mechanism by which the activity of the kinase is increased upon ethanol exposure. Such neuroadaptations could be part of a mechanism that leads to the development of excessive ethanol consumption.
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影响因子：
--
作者：
Grant, SGN
通讯作者：
Grant, SGN
影响因子：
4.7
作者：
Le, Hoa T.;Maksumova, Lola;Pallen, Catherine J.
通讯作者：
Pallen, Catherine J.
影响因子：
11.4
作者：
Lei, G;Xue, S;Yu, XM
通讯作者：
Yu, XM
影响因子：
56.9
作者：
Miyakawa, T;Yagi, T;Niki, H
通讯作者：
Niki, H
DOI：
10.1073/pnas.94.9.4761
发表时间：
1997-04-29
影响因子：
11.1
作者：
Kojima, N;Wang, J;Kandel, ER
通讯作者：
Kandel, ER