REGULATORY MECHANISMS IN PEPTIDERGIC NEURONS

本项目的总体目标是进一步了解 调节分泌产物产生的调节机制 在肽能神经元中。我们将使用神经分泌袋细胞， 作为这些研究的实验易处理的模型系统。我们 先前已经表明肽前体的合成 这些细胞产生的产卵激素（proELH）似乎与 由突触前输入和来自共分泌肽的反馈控制，和 这种控制是由细胞内信使（cAMP和Ca++）介导的。 考虑到这些信使系统对大脑功能的重要性， 这些细胞，以及它们与每个细胞相互作用的广泛记录的例子 另一方面，我们建议全面调查 袋细胞代谢中的细胞外和细胞内信使。我们将 集中在袋细胞分泌的肽和 生殖结构对ELH产生的影响;腺苷酸环化酶的作用 通过GTP结合蛋白激活和介导这种效应; 细胞内Ca++和蛋白激酶C介导其作用; 温度对这些过程和DNA结合作用的影响 蛋白质介导这些信使对proELH合成的作用。 此外，我们还将研究proELH加工的潜在调节作用， 和交通工具。预计这些研究将 加强我们对调节功能性疾病的基本机制的理解， 肽能神经元的活性。

The overall goal of this project is to further a basic understanding of the regulatory mechanisms that operate to regulate secretory product production in the peptidergic neuron. We will use the neurosecretory bag cells of Aplysia as an experimentally tractable model system for these studies. We have previously shown that synthesis of the precursor to the peptide egg-laying hormone (proELH) produced by these cells appears to be tightly controlled by presynaptic input and feedback from co-secreted peptides, and that this control is mediated by intracellular messengers (cAMP and Ca++). In view of the importance of these messenger systems to the function of these cells, and widely documented examples of their interactions with each other, we propose to undertake a comprehensive survey of the operation of extracellular and intracellular messengers in bag cell metabolism. We will focus on the influence of peptides secreted by bag cells and by reproductive structures on ELH production; on the role of adenylate cyclase activation and mediation of this effect by GTP-binding proteins; on intracellular Ca++ and mediation of its actions by protein kinase C; on the influence of temperature on these processes and on the role of DNA-binding proteins in mediating the actions of these messengers on proELH synthesis. In addition, we will study the potential regulation of proELH processing and transport by these agents. It is anticipated that these studies will enhance our understanding of the basic mechanisms regulating the functional activity of peptidergic neurons in general.