Membrane Targeting of ATP-sensitive Potassium Channel EFFECTS OF GLYCOSYLATION ON SURFACE EXPRESSION

摘要: Oligosaccharides play significant roles in trafficking, folding, and sorting of membrane proteins. Sulfonylurea receptors (SURx), members the ATP binding cassette family proteins, associate with inward rectifier Kir6.x to form ATP-sensitive potassium channels (K(ATP)). These are found on plasma many tissues a pivotal role synchronizing electrical excitability cell metabolic state. Trafficking defects resulting from three independent SUR1 mutations involved disease persistent hyperinsulinemic hypoglycemia infancy have been described. Two these displayed notable decreases glycosylation. Here we investigated relationship between two N-linked glycosylation sites (Asn(10) Asn(1050)) trafficking. Using patch clamp analysis, surface biotinylation, immunofluorescence microscopy, demonstrate decrease expression single or double site mutants (N10Q,N1050Q) when co-expressed Kir6.2. Additionally, show prominent retention within ER mutant under same conditions. Further investigation revealed that mutation signal was able partially restore mutant. studies suggest is key element for proper trafficking K(ATP) channels.