TY - JOUR T1 - A Novel Actin-Binding Domain on Slo1 Calcium-Activated Potassium Channels Is Necessary for Their Expression in the Plasma Membrane JF - Molecular Pharmacology JO - Mol Pharmacol SP - 359 LP - 368 DO - 10.1124/mol.107.039743 VL - 73 IS - 2 AU - Shengwei Zou AU - Smita Jha AU - Eun Young Kim AU - Stuart E. Dryer Y1 - 2008/02/01 UR - http://molpharm.aspetjournals.org/content/73/2/359.abstract N2 - Large-conductance Ca2+-activated K+ (BKCa) channels regulate the physiological properties of many cell types. The gating properties of BKCa channels are Ca2+-, voltage- and stretch-sensitive, and stretch-sensitive gating of these channels requires interactions with actin microfilaments subjacent to the plasma membrane. Moreover, we have previously shown that trafficking of BKCa channels to the plasma membrane is associated with processes that alter cytoskeletal dynamics. Here, we show that the Slo1 subunits of BKCa channels contain a novel cytoplasmic actin-binding domain (ABD) close to the C terminus, considerably downstream from regions of the channel molecule that play a major role in determining channel-gating properties. Binding of actin to the ABD can occur in a binary mixture in the absence of other proteins. Coexpression of a small ABD-green fluorescent protein fusion protein that competes with full-length Slo1 channels for binding to actin markedly suppresses trafficking of full-length Slo1 channels to the plasma membrane. In addition, Slo1 channels containing deletions of the ABD that eliminate actin binding are retained in intracellular pools, and they are not expressed on the cell surface. At least one point mutation within the ABD (L1020A) reduces surface expression of Slo1 channels to approximately 25% of wild type, but it does not cause a marked effect on the gating of point mutant channels that reach the cell surface. These data suggest that Slo1-actin interactions are necessary for normal trafficking of BKCa channels to the plasma membrane and that the mechanisms of this interaction may be different from those that underlie F-actin and stretch-sensitive gating. The American Society for Pharmacology and Experimental Therapeutics ER -