James Foster, Ph.D., Assistant Professor
Project: Regulation of membrane transporters by palmitoylation
Mentor: James Foster, Ph.D., Assistant Professor
Location: Department of Biomedical Sciences, School of Medicine & Health Sciences
Description: Department of Biomedical Sciences, School of Medicine & Health Sciences
Description: Over 5000 proteins have been identified as reversibly modified in the mammalian genome and evidence is growing which supports reversible palmitoylation as an important protein regulator. We have recently discovered that the dopamine transporter (DAT) and the sodium hydrogen ion exchanger isoform 1 (NHE1) is modified by S-palmitoylation, a post-translational modification in which C16 saturated palmitic acid is added to proteins via a thioester linkage to cysteine. S-palmitoylation of integral membrane proteins confers a variety of properties including control of activity, trafficking, turnover, and subcellular targeting. Palmitoylation is reversible and dynamic, conferring the ability of the protein to respond to physiological signals and participate in regulatory processes in a manner analogous to phosphorylation. In this project we are examining the role of palmitoylation in regulating DAT and NHE1 activity, subcellular trafficking, membrane microdomain localization, and degradation.
For DAT, dysfunction mediated by altered palmitoylation may result in imbalanced transmitter levels found in DA disorders including Parkinson's disease, schizophrenia, depression, and bipolar disorder. For NHE1, multiple cellular processes are associated with NHE1 activity including coordinated cell migration, cellular proliferation, and control of cell volume. NHE1 also functions as a membrane anchoring and scaffolding protein resulting in the formation of different protein complexes that participate in regulating signaling pathways within the cell. Altered NHE1 function via changes in palmitoylation may alter these processes. If remote participation is necessary because of COVID-19, students will be exposed to techniques and follow/direct experiments conducted by onsite personnel via live zoom. Students will analyze and plot the data using GraphPad Prism.
