The secretory vesicle protein synaptotagmin (Syt) has been proposed to function as a calcium sensor in regulated exocytosis and trigger membrane fusion via calcium-dependent interactions with phospholipids and the SNARE proteins syntaxin and SNAP25. The objective of this proposal is to determine the functional role of synaptotagmin in regulated exocytosis and to identify the biochemical properties responsible for its function.
The specific aims i nclude: to determine if synaptotagmin is the calcium sensor for regulated exocytosis in vivo; and to determine the regulatory role of Syt-SNARE interactions and Syt-phospholipid interactions in calcium-dependent exocytosis. A Syt-deficient PC12 cell line, which exhibits a loss of calcium-dependent exocytosis, will be utilized to test for the ability of Syt calcium binding, SNARE binding, and phospholipid binding mutants to rescue the loss of function. These studies will elucidate the mechanism by which Syt regulates exocytosis in a calcium dependent manner. Identifying Syt as the calcium-sensor for exocytosis and determining which properties of Syt are responsible for its regulatory function could lead to the development of drug strategies for the treatment of a number of endocrine and neural pathologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH075224-02
Application #
7085462
Study Section
Special Emphasis Panel (ZRG1-F03B (20))
Program Officer
Curvey, Mary F
Project Start
2005-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$30,903
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715