Protein kinase Mzeta is essential for the induction and maintenance of dopamine-induced long-term potentiation in apical CA1 dendrites.
Protein kinase Mzeta is essential for the induction and maintenance of dopamine-induced long-term potentiation in apical CA1 dendrites.
复制标题
DOI：
10.1101/lm.1991910
复制
发表时间：
2010-12
影响因子：
2
通讯作者：
Sheeja Navakkode;Sreedharan Sajikumar;T. Sacktor;J. Frey
中科院分区：
文献类型：
--
作者：
Sheeja Navakkode;Sreedharan Sajikumar;T. Sacktor;J. Frey
多巴胺能 D1/D5 受体介导的过程对于某些形式的记忆以及记忆的细胞模型、海马 CA1 区域的海马长时程增强 (LTP) 非常重要。 D1/D5 受体功能是通过激活 cAMP/PKA 途径诱导 CA1-LTP (L-LTP) 的蛋白质合成依赖性维持所必需的。在早期的研究中，我们报道了 L-LTP 的 D1/D5 受体功能和 N-甲基-D-天冬氨酸 (NMDA) 受体之间的协同相互作用。此外，我们还发现了传统电诱导的 L-LTP 需要非典型蛋白激酶 C 亚型、蛋白激酶 M z (PKM z)，其中 PKM z 已被确定为顶端 CA1 树突中的 LTP 特异性可塑性相关蛋白 (PRP)。在这里，我们研究了多巴胺能通路是否激活 PKM z。我们发现多巴胺 (DA) 的应用会引发蛋白质合成依赖性 LTP，需要协同 NMDA 受体激活和顶端 CA1 树突中的蛋白质合成。我们将 PKM 确定为 DA 诱导的 PRP，它通过突触标记过程对激活的突触输入发挥作用。
Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation of the cAMP/PKA-pathway. In earlier studies we had reported a synergistic interaction of D1/D5-receptor function and N-methyl-D-aspartate (NMDA)-receptors for L-LTP. Furthermore, we have found the requirement of the atypical protein kinase C isoform, protein kinase Mζ (PKMζ) for conventional electrically induced L-LTP, in which PKMζ has been identified as a LTP-specific plasticity-related protein (PRP) in apical CA1-dendrites. Here, we investigated whether the dopaminergic pathway activates PKMζ. We found that application of dopamine (DA) evokes a protein synthesis-dependent LTP that requires synergistic NMDA-receptor activation and protein synthesis in apical CA1-dendrites. We identified PKMζ as a DA-induced PRP, which exerted its action at activated synaptic inputs by processes of synaptic tagging.