The strong inward rectifier potassium channels are involved in action potential repolarization, modulation of cell excitability, and determination of cell resting potential in the brain and other excitable cells. Indeed, mutations in these channels are associated with defects in cell excitability, periodic paralysis, cardiac arrhythmias, and developmental abnormalities. Recently, it has been demonstrated that proteins that are associated with ion channels may modulate the functional properties of the channels, and such interactions may have profound implications in normal physiology and disease. Defects in channel-interacting proteins could lead to problems in channel expression, membrane targeting, association of channels with signaling complexes, and channel electrical activity. This proposal aims to identify and characterize the proteins that interact with inward rectifier potassium channels. Recently, we have identified such an interaction between inward rectifier channels and the scaffolding protein SAP97 in the brain. The goal of this project is to identify the complex of proteins that associate with inward rectifier potassium channels and to analyze the functional ability of these proteins to cluster, localize and regulate the activity of the channels.
| Fang, Yun; Schram, Gernot; Romanenko, Victor G et al. (2005) Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2. Am J Physiol Cell Physiol 289:C1134-44 |
| Leonoudakis, Dmitri; Conti, Lisa R; Anderson, Scott et al. (2004) Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2.x)-associated proteins. J Biol Chem 279:22331-46 |
| Romanenko, Victor G; Fang, Yun; Byfield, Fitzroy et al. (2004) Cholesterol sensitivity and lipid raft targeting of Kir2.1 channels. Biophys J 87:3850-61 |
| Leonoudakis, Dmitri; Conti, Lisa R; Radeke, Carolyn M et al. (2004) A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J Biol Chem 279:19051-63 |
