Ernest Gallo Research Center, University of California San Francisco, Emeryville, California, USA.
J Neurochem. 2011 Nov;119(4):879-89. doi: 10.1111/j.1471-4159.2011.07485.x. Epub 2011 Oct 11.
In vivo exposure of rodents to ethanol leads to a long-lasting increase in Fyn kinase activity in the dorsomedial striatum (DMS). In this study, 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 to 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.
体内暴露于乙醇会导致鼠类脑的背内侧纹状体（DMS）中 Fyn 激酶活性的持久增加。在这项研究中，我们旨在确定一种分子机制，该机制有助于 DMS 中 Fyn 活性对乙醇的增强。蛋白酪氨酸磷酸酶 α（PTPα）正向调节 Fyn 的活性，我们发现，反复全身给予乙醇或 binge 饮酒会导致 DMS 中 PTPα 的突触定位增加，而 Fyn 就位于该部位。我们还证明， binge 饮酒会导致 DMS 中的 Fyn 活性增加，以及 Fyn 和 PTPα 在脂筏中的共定位。最后，我们表明，在对大鼠进行条件性或非条件性乙醇暴露后，突触部分中酪氨酸磷酸化（即活性）的 PTPα 水平增加。总之，我们的结果表明，PTPα 在 DMS 中的重新分布到 Fyn 所在的隔室中是激酶活性在乙醇暴露时增加的潜在机制。这种神经适应性可能是导致过度饮酒发展的机制的一部分。
