AP-4 binds basolateral signals and participates in basolateral sorting in epithelial MDCK cells

Adaptors are heterotetrameric complexes that mediate the incorporation of cargo into transport vesicles by interacting with sorting signals present in the cytosolic domain of transmembrane proteins. Four adaptors, AP-1 (beta1, gamma, mu1A or mu1B, sigma1), AP-2 (beta2, alpha, mu2, sigma2), AP-3 (beta3, delta, mu3, sigma3) or AP-4 (beta4, epsilonc, mu4, sigma4), have been characterized(1,2). AP1 and AP-3 mediate sorting events at the level of the TGN and/or endosomes, whereas AP-2 functions in endocytic clathrin coated vesicle formation; no function is known so far for AP-4. Here, we show that AP-4 can bind different types of cytosolic signals known to mediate basolateral transport in epithelial cells. Furthermore, in MDCK cells with depleted mu4 protein levels, several basolateral proteins are mis-sorted to the apical surface, showing that AP-4 participates in basolateral sorting in epithelial cells.