Rethinking rafts

Polarised epithelial cells generate their polarity by trafficking newly synthesised proteins to either the apical or basolateral plasma membrane. A long-standing hypothesis proposes that proteins are directed to the apical surface by associating with lipid rafts through glycosyl-phosphatidylinositol (GPI) anchors. Nigel Hooper and his colleagues challenge this dogma by showing that, in the case of porcine membrane dipeptidase (MDP), N-glycan sidechains rather than a GPI anchor direct apical targeting in kidney epithelial cells (see p. 5079). MDP contains a GPI anchor site and two N-glycosylation sites. The authors show that, although MDP lacking a GPI anchor site is secreted instead of being attached to the cell surface, it is still targeted to the apical surface. By contrast, when its N-glycosylation sites are removed, MDP localises to the basolateral membrane, even though it still associates with lipid rafts. Other proteins may use O-glycans instead of N-glycans as apical targeting signals, suggest the authors, and further studies should determine whether specific glycan sequences are required for targeting.