UNC-18 and UNC-13 are presynaptic proteins involved in the synaptic vesicle exocytosis steps of docking, priming, and fusion. UNC-13 functions in priming, yet UNC-18 function is obscure. To determine if UNC-18 can function in either docking or fusion, the ordering of UNC-13 and UNC-18 interactions will be determined.
Four specific aims will be pursued. 1) To implicate UNC-18 in docking, syntaxin-complexes will be purified from wild type and unc-13 mutant C. elegans. An increased UNC-18 in the unc-13 background will implicate UNC-18 in vesicle docking. 2) To test for a fusion role, the synaptobrevin and SNAP-25 content of a syntaxin/UNC-18 co-complex will be measured. If UNC-18 is present in complexes containing the requisite SNARE proteins, then a fusion role is implicated. 3) To detect UNC-18 binding to open syntaxin, constitutively open syntaxin mutants will be TAP tagged and screened for the presence of UNC-18, SNAP- 25 and synaptobrevin. The presence of UNC-18 will demonstrate UNC-18 interacts with the open conformation of syntaxin. If SNAP-25 and synaptobrevin are also present, then a fusion role for UNC-18 will be further supported. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS051977-03
Application #
7226960
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Talley, Edmund M
Project Start
2005-04-01
Project End
2008-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$50,428
Indirect Cost
Name
University of Utah
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112