hERG K+ channel trafficking: the role of Cog4

University Of Wisconsin Madison, Madison WI

Investigators

Abstract

DESCRIPTION (provided by applicant): hERG voltage-gated potassium channels have been implicated in the determination of resting membrane potential, cell differentiation and spike-frequency adaptation in CNS neurons. Mutations of hERG result in alteration of cardiac IKr in human ventricular myocytes, and lead to long QT syndrome, a disease characterized by increased excitability and arrhythmic potential. An increasing body of evidence points to faulty trafficking as the underlying cause of disease development associated with hERG mutations. The proposed study utilizes biochemical assays and electrophysiological recordings to characterize and examine the importance of a direct interaction between hERG and Cog4, a cis-Golgi protein involved in ER-Golgi vesicle transport. This interaction is hypothesized to serve a cargo recognition function within the mechanism responsible for sorting membrane-bound proteins into the appropriate Golgi microdomains. Such sorting could have ramifications on trafficking kinetics throughout the remainder of the pathway, and would be expected to alter the ability of hERG to appropriately localize to/within the plasma membrane.