Critical Components in Regulated Secretion

Type of Award: Catalyst
Date Awarded: July 2010
Award End Date: June 2010
Amount Awarded: $ 200,000.00
PI(s): Aaron Turkewitz, PhD, UChicago; Scott Brady, PhD, UIC;

Abstract: Neurons require release of critical signaling molecules known as neurotrophins from their target neurons for survival and normal function. Disruptions in this pathway are thought to be a risk factor in diseases like Alzheimer's, depression, and bipolar disease. Although the regulated secretion of neurotrophins is critical to the development and maintenance of neurons, we do not fully understand how the secretory granules needed to deliver neurotrophins are generated or delivered to where they are needed. A better understanding of this process will illuminate the normal functioning of the neuron and may reveal important insights in how these pathways contribute to Alzheimer's and affective disorders. We know that critical steps involved in the generation secretory granules like those needed for neurotrophin storage are of ancient evolutionary origin, so we can use the power genetic tools and methods of analysis to identify and analyze these steps in a single-celled organism, Tetrahymena and using this information to define essential homologues involved in neurotrophin storage. By exploiting specific features of Tetrahymena, we have identified a set of genes that conserved in mammalian neurons and may illuminate the mechanisms of neurotrophin storage in human nerve cells, and we therefore propose to undertake a parallel study of these genes in Tetrahymena and in mammalian cells.