Regulation and immunohistochemical localization of βγ-stimulated adenylyl cyclases in mouse hippocampus
Regulation and immunohistochemical localization of βγ-stimulated adenylyl cyclases in mouse hippocampus
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DOI：
10.1523/jneurosci.19-01-00180.1999
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发表时间：
1999-01-01
影响因子：
5.3
通讯作者：
Storm, DR
中科院分区：
文献类型：
--
作者：
Baker, LP;Nielsen, MD;Storm, DR
突触可塑性的特定形式，如长时程增强（LTP），是由cAMP调节或需要cAMP的增加。各种腺苷酸环化酶同种型具有独特的调节特性，因此在给定的细胞类型或组织中响应会聚信号的cAMP增加受到所表达的腺苷酸环化酶同种型的特性的影响。在大多数组织中，腺苷酸环化酶活性由神经递质或激素通过刺激性G蛋白（G（s））偶联受体刺激，并通过抑制性G蛋白（G（i））连接受体抑制。然而，在海马中，G（i）偶联受体的刺激增强G（s）刺激的cAMP水平。这种效应可能与腺苷酸环化酶2型和4型（AC 2和AG 4）的调节特性有关，这些亚型在体外由G（i）的β-γ亚基增强。虽然AC 2已被证明在全细胞中被β-γ刺激，但描述AC 4在体内对β-γ敏感性的报道尚未出现。我们的研究结果表明，G（s）介导的刺激AG 4是加强β γ从激活的G（i）偶联受体在完整的人胚肾（HEK）293细胞释放。此外，我们表明，AG 2和AC 4蛋白在小鼠海马结构中表达，它们与MAP 2，树突状和/或突触后标记共定位。海马体中AC 2和AC 4的存在以及这些酶中的每一种检测G（s）和G（i）偶联受体的同时激活的能力表明，它们可能通过协调这种重叠的突触输入，在某些形式的突触可塑性中发挥关键作用。
Specific forms of synaptic plasticity such as long-term potentiation (LTP) are modulated by or require increases in cAMP. The various adenylyl cyclase isoforms possess unique regulatory properties, and thus cAMP increases in a given cell type or tissue in response to converging signals are subject to the properties of the adenylyl cyclase isoforms expressed. In most tissues, adenylyl cyclase activity is stimulated by neurotransmitters or hormones via stimulatory G-protein (G(s))-coupled receptors and is inhibited via inhibitory G-protein (G(i))-linked receptors. However, in the hippocampus, stimulation of G(i)-coupled receptors potentiates G(s)-stimulated cAMP levels. This effect may be associated with the regulatory properties of adenylyl cyclase types 2 and 4 (AC2 and AG4), isoforms that are potentiated by the beta gamma subunit of G(i) in vitro. Although AC2 has been shown to be stimulated by beta gamma in whole cells, reports describing the sensitivity of AC4 to beta gamma in vivo have yet to emerge. Our results demonstrate that G(s)-mediated stimulation of AG4 is potentiated by beta gamma released from activated G(i)-coupled receptors in intact human embryonic kidney (HEK) 293 cells. Furthermore, we show that the AG2 and AC4 proteins are expressed in the mouse hippocampal formation and that they colocalize with MAP2, a dendritic and/or postsynaptic marker. The presence of AC2 and AC4 in the hippocampus and the ability of each of these enzymes to detect coincident activation of G(s)- and G(i)-coupled receptors suggest that they may play a crucial role in certain forms of synaptic plasticity by coordinating such overlapping synaptic inputs.