Suppression of Tumor-related Glycosylation of Cell Surface Receptors by the 16-kDa Membrane Subunit of Vacuolar H+-ATPase

The glycosylation of integrins and other cell surface receptors is altered in many transformed cells. Notably, an increase in the number of β1,6-branched N-linked oligosaccharides correlates strongly with invasive growth of cells. An ectopic expression of the Golgi enzymeN-acetylglucosaminyltransferase V (GlcNAc-TV), which forms β1,6 linkages, promotes metastasis of a number of cell types. It is shown here that the 16-kDa transmembrane subunit (16K) of vacuolar H+-ATPase suppresses β1,6 branching of β1integrin and the epidermal growth factor receptor. Overexpression of 16K inhibits cell adhesion and invasion. 16K contains four hydrophobic membrane-spanning α-helices, and its ability to influence glycosylation is localized primarily within the second and fourth membrane-spanning α-helices. 16K also interacts directly with the transmembrane domain of β1 integrin, but its effects on glycosylation were independent of its binding to β1integrin. These data link cell surface tumor-related glycosylation to a component of the enzyme responsible for acidification of the exocytic pathway.