Potassium channel trafficking
Most ion channels function to pass ions across specific membranes in the cell, often the plasma membrane at the cell surface. The processes determining how, when, where and how many ion channels reach specific membranes, and how long they stay there before being internalized for recycling or degradation, are crucial factors in ion channel biology. Increasing attention is being paid to disease processes, inherited mutations and small molecules that impair channel protein movement, or 'trafficking', around the cell, and to potential therapeutic mechanisms targeting channel trafficking.
We are utilizing a range of tools including transgenic mouse models, confocal immunofluorescence microscopy, electrophysiology, protein chemistry and site-directed mutagenesis, to determine the mechanisms by which MiRPs - single transmembrane domain ancillary subunits - are trafficked, and how they impact trafficking of their larger, potassium channel alpha subunit partners.
Xu X, Kanda VA, Choi E, Panaghie G, Roepke TK, Gaeta SA, Christini DJ, Lerner DJ, Abbott GW. (2009) MinK-dependent internalization of the IKs potassium channel. Cardiovascular Research 82(3):430-8
Roepke TK, Kontogeorgis A, Ovanez C, Xu X, Young JB, Purtell K, Goldstein PA, Christini DJ, Peters NS, Akar FG, Gutstein DE, Lerner DJ, Abbott GW. (2008) Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f. FASEB J. 22(10):3648-60 PMID: 18603586