A late phase of cerebellar long-term depression requires activation of CaMKIV and CREB
A late phase of cerebellar long-term depression requires activation of CaMKIV and CREB
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DOI：
10.1016/s0896-6273(00)80808-9
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发表时间：
1999-07-01
期刊：
影响因子：
16.2
通讯作者：
Linden, DJ
中科院分区：
文献类型：
--
作者：
Ahn, S;Ginty, DD;Linden, DJ
最近，有研究表明，小脑LTD有一个可能被蛋白质合成抑制剂阻断的晚期。为了理解后期的机制，我们干扰了转录因子的激活，这些转录因子可能将突触激活与蛋白质合成结合起来。用编码CREB显性抑制形式的表达载体转染培养的浦肯野神经元，导致晚期几乎完全阻断。激活CREB的激酶被抑制，并评估LTD。抑制PKA或MAPK/RSK级联对晚期没有影响，而设计干扰CaMKIV功能的结构则减弱了晚期。这些结果表明CaMKIV和ORES的激活是建立小脑LTD晚期的必要条件。
Recently, it has been shown that cerebellar LTD has a late phase that may be blocked by protein synthesis inhibitors. To understand the mechanisms underlying the late phase, we interfered with the activation of transcription factors that might couple synaptic activation to protein synthesis. Particle-mediated transfection of cultured Purkinje neurons with an expression vector encoding a dominant inhibitory form of CREB resulted in a nearly complete blockade of the late phase. Kinases that activate CREB were inhibited, and LTD was assessed. Inhibition of PKA or the MAPK/RSK cascades were without effect on the late phase, while constructs designed to interfere with CaMKIV function attenuated the late phase. These results indicate that the activation of CaMKIV and ORES are necessary to establish a late phase of cerebellar LTD.