VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells

Apical proteins are sorted and delivered from the trans-Golgi network to th e plasma membrane by a mechanism involving sphingolipid-cholesterol rafts. In this paper, we report the effects of changing the levels of VIP17/MAL, a tetraspan membrane protein localized to post-Golgi transport containers an d the apical cell surface in MDCK cells, Overexpression of VIP17/MAL distur bed the morphology of the MDCK cell layers by increasing apical delivery an d seemingly expanding the apical cell surface domains. On the other hand, e xpression of antisense RNA directed against VIP17/MAL caused accumulation i n the Golgi and/or im paired apical transport of different apical protein m arkers, i,e,, influenza virus hemagglutinin, the secretory protein clusteri n (gp80), the transmembrane protein gp114, and a glycosylphosphatidylinosit ol-anchored protein, However, antisense RNA expression did not affect the d istribution of E-cadherin to the basolateral surface. Because VIP17/MAL ass ociates with sphingolipid-cholesterol rafts, these data provide functional evidence that this protein is involved in apical transport and might be a c omponent of the machinery clustering lipid rafts with apical cargo to form apical transport carriers.