The goal of this project is to clone the high affinity choline uptake carrier (HACU), an important molecular reagent for understanding cholinergic mechanism during normal aging process and under several pathological conditions such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS). Cholinergic neurotransmission in the central nervous system is involved in many fundamental brain processes such as learning, arousal and sleep, which undergo age related alterations. The formation of the neurotransmitter acetylcholine is catalyzed by the enzyme choline acetyltransferase (ChAT, E.C. 2.3.1.6), which transfers acetyl group from acetylcoenzyme A to choline, in the presynaptic nerve terminals of cholinergic neurons. Acetylcholine is packaged into the synaptic vesicles by a vesicular acetylcholine transporter (VAChT) and is then ready to be released in a calcium dependent manner. Acetylcholine binds specifically to either the nicotinic or muscarinic receptors to transmit information to the postsynaptic neurons. The action of acetylcholine is terminated through hydrolysis to acetate and choline by the enzyme acetylcholinesterase (ACHE, E.C.3.1.1.7). Most of the choline is then transported back to the presynaptic terminal to be recycled as one of the precursors for the biosynthesis of the neurotransmitter acetylcholine. This step, which is mediated by the action of the high affinity choline uptake system (HACU), is believed to be the rate limiting step in the biosynthesis of acetylcholine. Therefore, molecular analysis of the HACU is crucial for further understanding of how cholinergic mechanism operates in the central nervous system and is regulated under physiological and pathological conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
7R03AG015688-02
Application #
6039729
Study Section
Special Emphasis Panel (ZAG1-BJS-3 (J9))
Project Start
1998-04-01
Project End
2000-03-31
Budget Start
1999-01-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Florida
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Shi, J D; Kukar, T; Wang, C Y et al. (2001) Molecular cloning and characterization of a novel mammalian endo-apyrase (LALP1). J Biol Chem 276:17474-8