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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027150-03
Application #
3413344
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1990-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Berry, R W (1996) Modulation of adenylyl cyclase by Aplysia bag cell peptides: evidence for a common receptor. Brain Res Mol Brain Res 38:176-8
Berry, R W; Hanu, R; Redman, R S et al. (1994) Determinants of potency and temperature-dependent function in the Aplysia bag cell peptides. Peptides 15:855-60
Redman, R S; Berry, R W (1993) Temperature-dependent stimulation and inhibition of adenylate cyclase by Aplysia bag cell peptides. Brain Res Mol Brain Res 17:245-50
Redman, R S; Berry, R W (1992) ProELH-related peptides: influence on bag cell cAMP levels. Brain Res Mol Brain Res 15:216-20
Redman, R S; Berry, R W (1991) Temperature-dependent peptidergic feedback: potential role in seasonal egg laying in Aplysia. J Neurosci 11:1780-5