Apical secretion and sialylation of soluble dipeptidyl peptidase IV are two related events

The role of glycans in the apical targeting of proteins in epithelial cells remains a debated question. me have expressed the mouse soluble dipeptidyl peptidase IV (DPP TV ectodomain) in kidney (MDCK) and in intestinal (Caco- 2) epithelial cell lines, as a model to study the role of glycosylation in apical targeting. The mouse DPP IV ectodomain was secreted mainly into the apical medium by MDCK cells. Exposure of MDCK cells to GalNac-alpha-O-benzy l, a drug previously described as an inhibitor of mucin O-glycosylation, pr oduced a protein with a lower molecular weight. in addition this treatment resulted in a decreased apical secretion and an increased basolateral secre tion of mouse DPP TV ectodomain. When expressed in Caco-2 cells, the mouse DPP TV ectodomain was secreted mainly into the basolateral medium. However, BGN was still able to decrease the amount of apically secreted protein and to increase its basolateral secretion. Neuraminidase digestion showed that the most stricking effect of BGN was a blockade of DPP IV sialylation in b oth MDCK and Caco-2 cells. These results indicate that a specific glycosyla tion step, namely, sialylation, plays a key role in the control of the apic al targeting of a secreted DPP IV both in MDCK and Caco-2 cells. (C) 2000 A cademic Press.