Differential asparagine-linked glycosylation of voltage-gated K+ channels in mammalian brain and in transfected cells

Glycosylation of ion channel proteins dramatically impacts channel function . Here we characterize the asparagine (N)-linked glycosylation of voltage-g ated K+ channel a subunits in rat brain and transfected cells. We find that in brain Kv1.1, Kv1.2 and Kv1.4, which have a single consensus glycosylati on site in the first extracellular interhelical domain, are N-glycosylated with sialic acid-rich oligosaccharide chains. Kv2.1, which has a consensus site in the second extracellular interhelical domain, is not N-glycosylated . This pattern of glycosylation is consistent between brain and transfected cells, providing compelling support for recent models relating oligosaccha ride addition to the location of sites on polytopic membrane proteins. The extent of processing of N-linked chains on Kv1.1 and Kv1.2 but not Kv1.4 ch annels expressed in transfected cells differs from that seen for native bra in channels, reflecting the different efficiencies of transport of K+ chann el polypeptides from the endoplasmic reticulum to the Golgi apparatus. Thes e data show that addition of sialic acid-rich N-linked oligosaccharide chai ns differs among highly related K+ channel alpha subunits, and given the es tablished role of sialic acid in modulating channel function, provide evide nce for differential glycosylation contributing to diversity of K+ channel function in mammalian brain.