REGULATORY MECHANISMS IN PEPTIDERGIC NEURONS

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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.