It is our goal to continue our molecular and genetic analysis of synaptic transmission in the soil nematode Caenorhabditis elegans. C. elegans is being used for these studies because of its simple nervous system, its ease of genetic and molecular analysis, and the complete sequencing of its genome. The proposed research is based on recent results and on recent technological advances. The three broad goals are: (1) to analyze in depth the recently-described rip-1 gene, which encodes an extremely large protein thought to provide a """"""""molecular scaffold"""""""" for the components of a presynaptic nerve terminal; (2) to begin an investigation of the mechanisms used within nerve terminals to regulate the amount of neurotransmitter packaged into each synaptic vesicle; and (3) to continue studies using a C. elegans cell culture system for the analysis of synaptic development and function in vitro. The proposed studies will extend our previous analysis of synaptic structure and neurotransmitter function in the soil nematode Caenorhabditis elegans, and will include the isolation of mutants deficient in the regulation of vesicle content, and the identification of specific molecules and signaling pathways required for proper modulation of quantal size. Although this is basic research, it is clearly relevant to health, since proper neurotransmitter release is crucial to proper function of the nervous system, and defective transmitter release has been implicated in many psychiatric and neurological disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059642-10
Application #
6747302
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Tompkins, Laurie
Project Start
1994-08-01
Project End
2007-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
10
Fiscal Year
2004
Total Cost
$331,100
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Mullen, Gregory P; Grundahl, Kiely M; Gu, Mingyu et al. (2012) UNC-41/stonin functions with AP2 to recycle synaptic vesicles in Caenorhabditis elegans. PLoS One 7:e40095
Jung, Nadja; Wienisch, Martin; Gu, Mingyu et al. (2007) Molecular basis of synaptic vesicle cargo recognition by the endocytic sorting adaptor stonin 2. J Cell Biol 179:1497-510
Mathews, Eleanor A; Mullen, Gregory P; Crowell, John A et al. (2007) Differential expression and function of synaptotagmin 1 isoforms in Caenorhabditis elegans. Mol Cell Neurosci 34:642-52
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
Loria, Paula M; Duke, Angie; Rand, James B et al. (2003) Two neuronal, nuclear-localized RNA binding proteins involved in synaptic transmission. Curr Biol 13:1317-23