N-glycans as apical sorting signals in epithelial cells

In epithelial Madin-Darby canine kidney (MDCK) cells newly synthesized molecules are sorted in the trans-Golgi network and directly delivered to their apical and basolateral surface destinations. Sorting is mediated by signals in the cytoplasmic domains of basolateral transmembrane proteins whereas glycosylphosphatidylinositol-linked proteins have apical sorting information in their glycolipid tails. Signals for apical transmembrane proteins are thought to reside in their ectodomains, because truncated forms lacking the cytoplasmic tail and the membrane anchor are secreted apically. Here we demonstrate that carbohydrates act as an apical targeting signal for secretory proteins. Growth hormone, which is non-glycosylated and secreted from both sides of MDCK cell layers, is secreted from the apical side when glycosylated. Thus glycans not only play a general role in protein folding but also appear to function in protein sorting in biosynthetic traffic.