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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020440-03
Application #
3400771
Study Section
Biochemistry Study Section (BIO)
Project Start
1983-06-01
Project End
1986-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
New York Medical College
Department
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595