The long-term goal of the proposed research is to determine the genetic and molecular bases of cholinergic neuronal function in the soil nematode Caenorhabditis elegans. The focus of the present research is on the cholinergic locus, which contains 2 genes: cha-1 is the structural gene for choline acetyltransferase (ChAT), the enzyme which synthesizes the neurotransmitter acetylcholine, and unc-17 is the gene which encodes the synaptic vesicle acetylcholine transporter. The research has 6 primary aims: 1) To study the development of the cholinergic nervous system during embryonic and postembryonic development by monitoring the appearance of cholinergic markers. 2, 3) To identify trans-acting factors involved in the control and expression of the cholinergic phenotype. 4, 5) To study the contribution of specific classes of cholinergic neurons to the overall function of the nervous system and behavior of the organism. 6) To investigate the role of a neuron's transmitter on the development of the neuron. The proposed research will provide a molecular and genetic analysis of how neurons become cholinergic neurons and should elucidate the processes by which neurons become differentiated and achieve a common neurotransmitter identity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM038679-13
Application #
6018699
Study Section
Special Emphasis Panel (ZRG1-NLS-1 (02))
Project Start
1989-12-01
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Mathews, Eleanor A; Mullen, Gregory P; Manjarrez, Jacob R et al. (2015) Unusual regulation of splicing of the cholinergic locus in Caenorhabditis elegans. Genetics 199:729-37
Mathews, Eleanor A; Mullen, Gregory P; Hodgkin, Jonathan et al. (2012) Genetic interactions between UNC-17/VAChT and a novel transmembrane protein in Caenorhabditis elegans. Genetics 192:1315-25
Duerr, Janet S; Han, He-Ping; Fields, Stephen D et al. (2008) Identification of major classes of cholinergic neurons in the nematode Caenorhabditis elegans. J Comp Neurol 506:398-408
Mullen, Gregory P; Mathews, Eleanor A; Vu, Mai H et al. (2007) Choline transport and de novo choline synthesis support acetylcholine biosynthesis in Caenorhabditis elegans cholinergic neurons. Genetics 177:195-204
Rand, James B (2007) Acetylcholine. WormBook :1-21
Sandoval, Gisela M; Duerr, Janet S; Hodgkin, Jonathan et al. (2006) A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans. Nat Neurosci 9:599-601
Duerr, J S; Gaskin, J; Rand, J B (2001) Identified neurons in C. elegans coexpress vesicular transporters for acetylcholine and monoamines. Am J Physiol Cell Physiol 280:C1616-22
Lickteig, K M; Duerr, J S; Frisby, D L et al. (2001) Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its transcriptional corepressor UNC-37/groucho in Caenorhabditis elegans cholinergic motor neurons. J Neurosci 21:2001-14
Zhu, H; Duerr, J S; Varoqui, H et al. (2001) Analysis of point mutants in the Caenorhabditis elegans vesicular acetylcholine transporter reveals domains involved in substrate translocation. J Biol Chem 276:41580-7
Rand, J B; Duerr, J S; Frisby, D L (2000) Neurogenetics of vesicular transporters in C. elegans. FASEB J 14:2414-22

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