Hippocampal neurons express a calcineurin-activated adenylyl cyclase
Hippocampal neurons express a calcineurin-activated adenylyl cyclase
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DOI：
10.1523/jneurosci.2376-05.2005
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发表时间：
2005-10-26
影响因子：
5.3
通讯作者：
Storm, DR
中科院分区：
文献类型：
--
作者：
Chan, GCK;Tonegawa, S;Storm, DR
Ca2+刺激的腺苷酸环化酶对几种形式的神经可塑性很重要，因为它们将活性依赖性Ca2+增加与神经元中的cAMP偶联。例如，钙调素刺激的腺苷酸环化酶AC1和AC8是依赖于海马的记忆和持久的长时程增强所必需的。为了确定腺苷酸环化酶的Ca2+刺激的其他机制，分析了来自缺乏AC1和AC8的转基因小鼠[双敲除（DKO）小鼠]的培养海马神经元的细胞内cAMP的Ca2+刺激。令人惊讶的是，来自DKO小鼠的神经元显示出显著的Ca 2+刺激的cAMP积累，其被钙调磷酸酶[PP2B（蛋白磷酸酶2B）]（一种Ca 2+活化的蛋白磷酸酶）的抑制剂阻断。对来自钙调神经磷酸酶-/-小鼠的培养神经元的分析证实，海马神经元表现出钙调神经磷酸酶依赖性cAMP增加，这可能有助于某些形式的神经可塑性。
Ca2+ -stimulated adenylyl cyclases are important for several forms of neuroplasticity because they couple activity-dependent Ca2+ increases to cAMP in neurons. For example, the calmodulin-stimulated adenylyl cyclases, AC1 and AC8, are required for hippocampus-dependent memory and long-lasting long-term potentiation. To identify other mechanisms for Ca2+ stimulation of adenylyl cyclases, cultured hippocampal neurons from transgenic mice lacking both AC1 and AC8 [ double knock-out (DKO) mice] were analyzed for Ca2+ stimulation of intracellular cAMP. Surprisingly, neurons from DKO mice showed significant Ca2+ -stimulated cAMP accumulation that was blocked by inhibitors of calcineurin [PP2B (protein phosphatase 2B)], a Ca2+ -activated protein phosphatase. Analysis of cultured neurons from calcineurin -/- mice confirmed that hippocampal neurons exhibit a calcineurin-dependent cAMP increase, which may contribute to some forms of neuroplasticity.