Ho N, Liauw J A, Blaeser F, Wei F, Hanissian S, Muglia L M, Wozniak D F, Nardi A, Arvin K L, Holtzman D M, Linden D J, Zhuo M, Muglia L J, Chatila T A
Department of Pediatrics, the Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurosci. 2000 Sep 1;20(17):6459-72. doi: 10.1523/JNEUROSCI.20-17-06459.2000.
The Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca(2+) signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca(2+)/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These results support an important role for CaMKIV/Gr in Ca(2+)-regulated neuronal gene transcription and synaptic plasticity and suggest that the contribution of other signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.
钙离子/钙调蛋白依赖性蛋白激酶IV/Gr（CaMKIV/Gr）是神经元钙信号传导的关键效应器；通过对小鼠进行靶向基因敲除分析其功能。缺乏CaMKIV/Gr的小鼠表现出神经元环磷酸腺苷反应元件结合蛋白（CREB）磷酸化受损以及钙离子/CREB依赖性基因表达受损。它们还缺乏两种形式的突触可塑性：海马CA1神经元中的长时程增强（LTP）和小脑浦肯野神经元中的晚期长时程抑制。然而，尽管LTP和CREB激活受损，但缺乏CaMKIV/Gr的小鼠在空间学习和记忆方面没有表现出明显缺陷。这些结果支持CaMKIV/Gr在钙离子调节的神经元基因转录和突触可塑性中起重要作用，并表明其他信号通路的作用可能使缺乏CaMKIV/Gr的小鼠的空间记忆得以保留。
