Vashisht Anirudh, Bach Svitlana V, Fetterhoff Dustin, Morgan James W, McGee Maria, Hegde Ashok N
Department of Neurobiology and Anatomy & Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, 27157, USA; Department of Biological and Environmental Sciences, Georgia College and State University, Milledgeville, GA, 31061, USA.
Department of Neurobiology and Anatomy & Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
Neurosci Lett. 2018 Nov 20;687:31-36. doi: 10.1016/j.neulet.2018.09.017. Epub 2018 Sep 13.
Proteolysis by the ubiquitin-proteasome pathway has pleiotropic effects on both induction and maintenance of long-term synaptic plasticity. In this study, we examined the effect of proteasome inhibition on signaling to the nucleus during late-phase long-term potentiation. When a subthreshold L-LTP induction protocol was used, proteasome inhibition led to a significant increase in phosphorylated CREB (pCREB) in the nucleus. Inhibitors of cAMP-dependent protein kinase/protein kinase A, extracellular signal-regulated kinase and cGMP-dependent protein kinase/protein kinase G all blocked the proteasome-inhibition-mediated increase in nuclear pCREB after subthreshold stimulation. These results lay the groundwork for understanding a novel role for the proteasome in limiting signaling to the nucleus in the absence of adequate synaptic stimulation.
泛素-蛋白酶体途径介导的蛋白水解对长期突触可塑性的诱导和维持具有多效性作用。在本研究中，我们检测了蛋白酶体抑制对晚期长时程增强过程中向细胞核信号传导的影响。当使用阈下L-LTP诱导方案时，蛋白酶体抑制导致细胞核中磷酸化CREB（pCREB）显著增加。环磷酸腺苷依赖性蛋白激酶/蛋白激酶A、细胞外信号调节激酶和环磷酸鸟苷依赖性蛋白激酶/蛋白激酶G的抑制剂均能阻断阈下刺激后蛋白酶体抑制介导的细胞核pCREB增加。这些结果为理解蛋白酶体在缺乏足够突触刺激时限制向细胞核信号传导的新作用奠定了基础。
