REGULATION OF NEURONAL ACETYLCHOLINE RECEPTOR GENES

神经型烟碱型乙酰胆碱受体(NAChRs)由 结合(α)和结构(β)亚单位。不同的组合 的α和β亚基产生不同的nAChR亚型 药理和离子传导性能。转录的 调节可能是一个重要的决定因素的受体亚型 从而影响通过神经节或神经节的传递 通过控制nAChR亚型(S)出现在中枢神经系统的神经元群。 我们选择重点研究alpha3和alpha4基因的调控。 因为它们分别代表主要的神经节细胞和中枢神经系统 配体结合亚单位基因；它们都被证明是受调控的 在RNA水平上，通过细胞接触或NGF和TPA等因素； 在大鼠α3的情况下，细胞特异性至少在 部分在转录水平上。Alpha3和Alpha4发起人将 进行鉴定和测序。PC12细胞将用于生化和 识别相互作用的DNA结合蛋白的分子遗传学研究 可能参与了nAChR基因的调控 表情。大鼠颈上神经节(SCG)神经元将用于 补充启动子和转录因子的研究 尼古丁、神经生长因子、TPA及细胞间接触对大鼠肺损伤的影响 几个nAChR亚单位基因的表达。了解如何 这些nAChR基因是受调控的，亚型的表达 控制，将导致深入了解尼古丁如何在 神经系统。控制这些基因表达的机制 基因也可能与神经元nAChR基因表达的调控有关 在神经系统的其他地方和这种多基因的其他成员 一家人。

Neuronal nicotinic acetylcholine receptors (nAChRs) are composed of binding (alpha) and structural (beta) subunits. Different combinations of alpha and beta subunits produce nAChR subtypes with different pharmacological and ion conducting properties. Transcriptional regulation may be an important determinant of receptor subtype in a neuronal population and thus influence transmission through a ganglia or group of neurons in the CNS by controlling the nAChR subtype(s) present. We have chosen to focus on the regulation of the alpha3 and alpha4 genes because they represent, respectively, the predominant ganglionic and CNS ligand binding subunit genes; they both have been shown to be regulated at the RNA level by cell contact or factors such as NGF and TPA; and in the case of the rat alpha3, cell-specificity is regulated at least in part at the transcriptional level. The alpha3 and alpha4 promoters will be identified and sequenced. PC12 cells will be used for biochemical and molecular genetic studies to identify DNA-binding proteins that interact with the alpha3 promoter and may be involved in the control of nAChR gene expression. Rat superior cervical ganglion (SCG) neurons will be used to complement the promoter and transcription factor studies in an examination of the effects of nicotine, NGF, TPA and cell-cell contact on the expression of several nAChR subunit genes. An understanding of how these nAChR genes are regulated and the expression of subtypes controlled, will lead to insight into how nicotine produces effects in the nervous system. The mechanisms that control the expression of these genes may also be relevant to control of neuronal nAChR gene expression elsewhere in the nervous system and for other members of this multigene family.