TIP47 - A CARGO SELECTION DEVICE FOR MANNOSE 6-PHOSPHATE RECEPTOR TRAFFICKING

Mannose B-phosphate receptors (MPRs) transport newly synthesized lysos omal hydrolases from the Golgi to prelysosomes and then return to the Golgi for another round of transport. We have identified a 47 kDa prot ein (TIP47) that binds selectively to the cytoplasmic domains of catio n-independent and cation-dependent MPRs. TIP47 is present in cytosol a nd on endosomes and is required for MPR transport from endosomes to th e trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenyla lanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. Thes e data suggest that TIP47 binds MPR cytoplasmic domains and facilitate s their collection into transport vesicles destined for the Golgi.