|Start Date / Time||September 2, 2015 at 9:00 AM|
|End Date / Time||September 2, 2015 at 9:55 AM|
|Location||512 Light Hall|
|Presenter Name||Matthew Dickerson, PhD (Jacobson's lab)|
|Presentation Title||"Uncovering Regulatory Mechanisms of the Diabetes Associated Potassium Channel, TALK-1"|
|Status||This meeting has already occurred|
Glucose stimulated insulin secretion (GSIS) is critical for the maintenance of glucose homeostasis. GSIS depends on calcium influx into pancreatic beta cells, which is controlled by ion channels. Recently, a nonsynonymous polymorphism in the most highly expressed islet-specific potassium channel, TALK-1, has been associated with an increased risk of developing type-2 diabetes. Thus, we investigated the physiological regulation of TALK-1 channels to increase our understanding of mechanisms that modulate GSIS. Utilizing a membrane specific yeast two-hybrid assay we found that osteopontin interacts with TALK-1 and increases potassium flux through the channel in a phosphorylation dependent manner. We also determined that N-terminal palmitoylation of TALK-1 serves to limit its potassium flux, whereas lysophospholipase-1 (Lypla1) cleavage of palmitate from the channel increases potassium flux. These findings suggest that osteopontin binding as well as N-terminal palmitoylation of TALK-1 channels may serve to regulate beta cell calcium entry and GSIS.