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A. Specific Aims Presynaptic terminals are key sites for neural integration every bit as complex as their postsynaptic targets and
 

Summary: A. Specific Aims
Presynaptic terminals are key sites for neural integration every bit as complex as their postsynaptic targets and
G protein-coupled receptors (GPCRs) provide a key component of this neural plasticity. These receptors that
respond to every variety of neuromodulator and transmitter including glutamate, dopamine, acetylcholine,
GABA and 5-HT can depress neurotransmitter release by complex second messenger pathways, but also by
rapidly acting membrane delimited mechanisms. Mechanisms of presynaptic integration remain poorly
understood because the presynaptic terminals are largely inaccessible. Using unparalleled access afforded by
the lamprey giant synapse, we have recently demonstrated a potent, membrane-delimited mechanism by
which G inhibits neurotransmission by a direct action on the SNARE complex. We propose to determine
whether G and Ca2+
-synaptotagmin show a mutually antagonistic competition for interaction with the SNARE
complex. We seek to demonstrate that, because G competes with Ca2+
-synaptotagmin binding, GPCR-
mediated presynaptic inhibition is dynamically controlled by activity induced presynaptic Ca2+
signaling. Our
current hypothesis is that G competes with Ca2+
-synaptotagmin binding to the SNARE complex to effect
presynaptic inhibition, which leads ultimately to inhibition of synaptic vesicle fusion at the presynaptic terminal.
Specific Aim 1: To investigate G and Ca2+
synaptotagmin competition at SNARE complexes. We will

  

Source: Alford, Simon - Department of Biological Sciences, University of Illinois at Chicago

 

Collections: Biology and Medicine