THE MAMMALIAN AP-3 ADAPTER-LIKE COMPLEX MEDIATES THE INTRACELLULAR-TRANSPORT OF LYSOSOMAL MEMBRANE-GLYCOPROTEINS

In mammalian cells, the mannose B-phosphate receptors (MPRs) and the l ysosomal glycoproteins, lysosomal-associated membrane protein (LAMP) I , lysosomal integral membrane protein (LIMP) II, are directly transpor ted from the trans-Golgi network to endosomes and lysosomes. While MPR traffic relies on the AP-1 adaptor complex, we report that proper tar geting of LAMP I and LIMP II to lysosomes requires the AP-3 adaptor-li ke complex. Overexpression of these proteins, which contain either a t yrosine- or a di-leucine-based-sorting motif, promotes AP-3 recruitmen t on membranes. Inhibition of AP-3 function using antisense oligonucle otides leads to a selective misrouting of both LAMP I and LIMP II to t he cell surface without affecting MPR trafficking. These results provi de evidence that AP-3 functions in the intracellular targeting of tran smembrane glycoproteins to lysosomes.