NEURAL REGULATION OF CHOLINERGIC PROTEINS

胆碱能蛋白的神经调节

基本信息

批准号：
2266182
负责人：
WILLIAM RANDALL
金额：
$ 8.68万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-12-01 至 1994-11-30
项目状态：
已结题

项目摘要

The correct postsynaptic organization of cholinergic proteins at the neuromuscular junction requires the initiation and maintenance of functional innervation. The molecular mechanisms by which the genes encoding these proteins are regulated are largely unknown. The long range goal of this project is to determine how innervation controls the synthesis and expression of one member of the cholinergic synapse. acetylcholinesterase (AChE). AChE comprises a complex family of oligomeric proteins that differ structurally and in their association with cellular and extracellular compartments. Little is known regarding how the diversity of these proteins is generated. As a first step in understanding the mechanisms regulating the generation of the multiple forms of AChE we have chosen to study the genetic basis contributing to the diversity. This will include determining the structural nature of the transcripts and gene(s) for AChE and associating the types of mRNA transcripts with the molecular forms of the enzyme generated by the cell. These basic studies will then be applied in examining how innervation influences the transcriptional and posttranscriptional control of AChE expression and localization. It is likely that the nerve acts to regulate the local activity of synaptic proteins through its influence on synapse associated nuclei. This is a major hypothesis which we will examine using AChE as the candidate cholinergic marker. This project will use in vitro muscle-nerve cocultures and in vivo studies of denervated and innervated muscle to determine how nervous input controls AChE expression.

正确的胆碱能蛋白的突触后组织神经肌肉连接需要启动和维护功能神经。基因的分子机制调节这些蛋白质的编码在很大程度上未知。远距离该项目的目标是确定神经如何控制综合和胆碱能突触的一个成员的表达。乙酰胆碱酯酶（ACHE）。 ACHE包括一个复杂的低聚家族结构上及其与细胞相关的蛋白质和细胞外室。关于多样性的方式知之甚少这些蛋白质是生成的。作为理解的第一步调节多种形式的酸痛的机制我们拥有选择研究造成多样性的遗传基础。这会包括确定转录本和基因的结构性用于ACHE并将mRNA转录的类型与分子相关联细胞产生的酶的形式。这些基础研究将是应用于检查神经如何影响转录和 ACHE表达和定位的转录后控制。这是神经可能调节突触的局部活动蛋白质通过其对突触相关核的影响。这是一个我们将使用ACHE作为候选人进行检查的主要假设胆碱能标记。该项目将使用体外肌肉培养并在体内研究被取代和神经支配的肌肉，以确定如何神经输入控制ACHE表达。