REGULATORY MECHANISMS IN PEPTIDERGIC NEURONS

本项目的总体目标是加深对 用来管理分泌性产品生产的监管机制 在肽能神经元中。我们将使用神经分泌袋细胞 Aplysia作为实验上易于处理的模型系统用于这些研究。我们 以前已经证明了多肽前体的合成 由这些细胞产生的产卵激素(ProELH)似乎紧密地 由突触前输入和来自共分泌肽的反馈控制，以及 这种控制是由细胞内信使(cAMP和钙离子)介导的。 鉴于这些信使系统对 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，我们建议全面调查该中心的运作。 袋子细胞代谢中的胞外和胞内信使。我们会 关注袋子细胞和细菌分泌的多肽的影响 生殖结构对ELH产生的影响；腺苷环化酶的作用 GTP结合蛋白对这一效应的激活和调节 细胞内钙离子及其由蛋白激酶C介导的作用 温度对这些过程和DNA结合作用的影响 调节这些信使在PRELH合成中的作用的蛋白质。 此外，我们还将研究PRELH加工的潜在调节 并由这些特工运送。预计这些研究将 提高我们对调节功能的基本机制的理解 一般情况下，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.