REGULATION OF BIOSYNTHESIS OF DOPAMINE-BETA-HYDROXYLASE

阐明了参与调节生物合成的机制， 多巴胺-β-羟化酶（DBH）是理解 控制去甲肾上腺素能神经元的发育和表达 系统 该研究将：1。表征生化 DBH亚基形式之间的差异（其中一种是可溶性的， 另一个膜结合），我最近成功地在 在PC 12嗜铬细胞瘤细胞系中分化。 的关系 将研究这两种形式之间的关系，如果它们相互转换， 特异性蛋白水解切割糖基化的改变， 将考虑磷酸化。 2.研究神经 生长因子、地塞米松和二丁酰环磷酸腺苷改变了 胸径亚基的分布。 3.检查功能意义 的DBH形式的变化，并确定这种现象是否 对嗜铬细胞瘤有特异性，也可能与调节胸径有关 在外周和中枢神经系统中，或血清DBH中。 4. 多巴胺-β-羟化酶合成亚细胞位点的确定 以及它在细胞中获得亚细胞定位的机制。 嗜铬细胞和突触囊泡的可溶性和膜成分。

Elucidating the mechanisms involved in the regulation of biosynthesis of dopamine-Beta-hydroxylase (DBH) is central in understanding factors controlling the development and expression of the noradrenergic neuronal system. The proposed research will: 1. Characterize the biochemical differences between the subunit forms of DBH (one of which is soluble and the other membrane-bound) which I have recently succeeded in differentiating in the PC12 pheochromocytoma cell line. The relationship between these 2 forms will be studied and if they are interconverted, alterations in specific proteolytic cleavage glycosylation and phosphorylation will be considered. 2. Study the mechanism by which nerve growth factor, dexamethasone and dibutyryl cyclic AMP alter the distribution of the DBH subunits. 3. Examine the functional significance of alterations in the DBH forms and determine whether this phenomenon is specific for pheochromocytoma or also can be related to regulation of DBH in vivo in the peripheral and central nervous system, or to serum DBH. 4. Determine the subcellular site of synthesis of dopamine-Beta-hydroxylase and the mechanism by which it obtains its subcellular localization in the soluble and membrane components of chromaffin and synaptic vesicles.