STRUCTURAL REQUIREMENTS FOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-IIINVARIANT CHAIN TRAFFICKING IN POLARIZED MADIN-DARBY CANINE KIDNEY-CELLS

The invariant chain (Ii) targets major histocompatibility complex clas s II molecules to an endocytic processing compartment where they encou nter antigenic peptides. Analysis of Ii-transferrin receptor chimeras expressed in polarized Madin-Darby canine kidney (MDCK) cells shows th at the Ii cytoplasmic tail contains a dihydrophobic basolateral sortin g signal, Met(16)-Leu(17), which is recognized in both the biosyntheti c and endocytic pathways, Pro(15)-Met(16)-Leu(17) has previously been identified as one of two dihydrophobic Ii internalization signals acti ve in non-polarized cells. Pro(15) is also required for endocytosis in MDCK cells but not for basolateral sorting, indicating that the inter nalization signal recognized at the plasma membrane is distinct from t he sorting signal recognized by basolateral sorting machinery. Another dihydrophobic sequence, Leu(7)-Ile(8), is required for rapid internal ization of the chimeric receptors in MDCK cells but not for basolatera l sorting, providing further evidence that the structural requirements for basolateral sorting and internalization differ. Deletion analysis suggests that basolateral sorting of newly synthesized Ii-TR chimeras is also mediated by the membrane-proximal region of the Ii cytoplasmi c tail. However, this region does not promote polarized basolateral re cycling, indicating that the structural requirements for polarized sor ting in the biosynthetic and endocytic pathways are not identical.