The goal of this project is to determine the role of Synaptotagmin (Syt) IV in the control of mammalian synaptic transmission. The 15 identified Syts comprise a family of calcium (Ca) binding proteins that generally regulate membrane trafficking events. Syts I, II, and IV are found in synaptic vesicle membranes, which suggests that these isoforms are important for neurotransmission. Recent evidence reveals that Syts I and II are primary Ca sensors for neurotransmission, but there is little consensus on the role of Syt IV. The Syt IV protein is strongly elevated following seizures and has diminished Ca binding relative to Syt I and other isoforms. This proposal focuses on two Specific Aims to determine the function of Syt IV.
Specific Aim 1 tests the hypothesis that Syt IV is a Ca sensor that is less effective than Syt I in promoting neurotransmitter release.
Specific Aim 2 tests the hypothesis that elevation of Syt IV (as occurs following seizure) reduces neurotransmission. The experimental design will employ viral-mediated Syt IV expression and electrophysiological measurement of neurotransmission in cultured mammalian neurons. Evidence in support of these hypotheses would suggest a neuroprotective role for Syt IV following seizures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS051906-02
Application #
7046135
Study Section
Special Emphasis Panel (ZRG1-F03B (20))
Program Officer
Talley, Edmund M
Project Start
2005-04-01
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
2
Fiscal Year
2006
Total Cost
$31,791
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Ting, Jonathan T; Kelley, Brooke G; Lambert, Talley J et al. (2007) Amyloid precursor protein overexpression depresses excitatory transmission through both presynaptic and postsynaptic mechanisms. Proc Natl Acad Sci U S A 104:353-8
Ting, Jonathan T; Kelley, Brooke G; Sullivan, Jane M (2006) Synaptotagmin IV does not alter excitatory fast synaptic transmission or fusion pore kinetics in mammalian CNS neurons. J Neurosci 26:372-80