Glycosylation allows cell-surface transport of an anchored secretory protein.

We have previously described the construction and expression of a hybrid gene encoding a membrane-anchored form of rat growth hormone. This protein is anchored in cellular membranes by a carboxy-terminal extension composed of the transmembrane and cytoplasmic domains of the vesicular stomatitis virus glycoprotein. The protein is transported efficiently to the Golgi apparatus but not to the cell surface. To examine the possibility that N-linked glycosylation might be required for protein transport to the cell surface, we created two mutant proteins (using in vitro mutagenesis) in which single amino acids at two random sites in anchored growth hormone were changed to generate consensus sequences required for addition of N-linked carbohydrate. These mutant proteins, and a protein with both glycosylation sites, were glycosylated and were transported to the cell surface. These results suggest that N-linked glycosylation can serve as a signal for protein transport to the cell surface.