Functional Analysis of Synaptotagmin Domain Structure

Colorado State University, Fort Collins CO

Investigators

Abstract

Communication between neurons in the brain requires efficient calcium-triggered release of neurotransmitter from active neurons. Since the mechanisms of transmitter release have been highly conserved throughout evolution, molecular-genetic studies in fruit flies can reveal how mammalian neurons communicate without the expense or ethical considerations of mammalian studies. The current NSF project will examine how the neuronal calcium-binding protein, synaptotagmin, couples increased intra-neuronal calcium with neurotransmitter release. Synaptotagmin exhibits calcium-dependent interactions with cell membranes as well as with specific proteins. Using molecular techniques to generate mutant transgenic Drosophila, Dr. Reist and colleagues will determine the interactions that couple calcium-binding to efficient transmitter release. Actively adjusting the amount of transmitter released is thought to be a key mechanism mediating learning and memory in higher organisms. Thus, this work will provide critical scientific background required for translational studies aimed at improving neuronal communication in cases of neural dysfunction such as Alzheimer's disease. All transgenic fly lines generated will be made freely available to the scientific community. Dr. Reist has trained numerous undergraduate and graduate students and the implementation of this project will provide continued training opportunities for U.S. students. In addition, Dr. Reist participates in the International Brain Research Organization's visiting lecture team program and has taught students in China and Nigeria about the molecular mechanisms of transmitter release. As such, these studies will directly contribute to educational outreach in developing countries as well as within the United States.