REGULATION OF NEURONAL ACETYLCHOLINE RECEPTOR GENES

神经元烟碱乙酰胆碱受体（nAChR）由以下组成： 结合（α）和结构（β）亚基。 不同组合 α和β亚基的结合产生不同的nAChR亚型， 药理学和离子传导性质。 转录 调节可能是一个重要的决定因素受体亚型在一个 神经元群体，从而影响通过神经节的传输，或 通过控制nAChR亚型的存在，调节CNS中的神经元组。 我们选择专注于α 3和α 4基因的调控 因为它们分别代表了主要的神经节和CNS 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因子如NGF和TPA;以及 在大鼠α 3细胞特异性的情况下， 在转录水平上。 α 3和α 4启动子将 进行鉴定和测序 PC 12细胞将用于生化和 分子遗传学研究，以确定DNA结合蛋白， 可能参与nAChR基因的调控 表情 大鼠上级颈神经节（SCG）神经元将用于 补充启动子和转录因子的研究， 检查尼古丁、NGF、TPA和细胞-细胞接触对 几个nAChR亚基基因的表达。 了解如何 这些nAChR基因受到调节， 控制，将导致深入了解尼古丁如何产生影响， 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基因表达的控制有关 在神经系统的其他地方以及这个多基因的其他成员 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.