Dr. Joy A Umbach
PositionAdjunct Associate Professor
Research in my lab focuses on the molecular mechanism of neurotransmitter release. Central to this task is determining the role of specific proteins that participate in this process. One such protein is a novel synaptic vesicle constituent known as a cysteine string protein (csp). Using a variety of techniques including expression of cRNA in frog oocytes, electrophysiology, functional studies of mutant alleles of Drosophila and fluorescence imaging of calcium dynamics in presynaptic boutons, we have shown that csps are essential for the evoked release of neurotransmitter and that csps interact with the calcium channels that trigger release. To extend this work we are using co-cultures of Xenopus nerve and muscle cells. This preparation has the advantage that reagents (peptides, antibodies, enzymes) can be applied intracellularly via a patch pipette. One can then use electrophysiological and imaging approaches to characterize the effect of these agents on synaptic transmission and calcium channel function. In addition to understanding of the role of csps (and proteins with which csps interact) in presynaptic events, we have become interested in the mechanism by which lithium (Li) and other mood stabilizing drugs affect presynaptic function. This work is based on our findings that therapeutic levels of Li ions selectively up-regulate csp gene expression in both rat brain and differentiated PC12 cell cultures. We are using amperometry and radio-tracer flux measurements on PC12 cells to assay the functional consequences of this enhanced gene expression. In situ hybridization assays of rat brain are defining specific brain regions affected by drug treatment. Moreover, intracellular Li ion-sensitive electrodes and reporter protein assays are being used to gain insight into the mechanism by which Li and other drugs enhance gene expression. Ultimately, this work may afford insights into the cause and improved treatment of bipolar-affective disorders.
Lab MembershipsUmbach Lab (Principal Investigator/Director)
Los Angels, CA