THE CYTOPLASMIC TAIL OF LYSOSOMAL ACID-PHOSPHATASE CONTAINS OVERLAPPING BUT DISTINCT SIGNALS FOR BASOLATERAL SORTING AND RAPID INTERNALIZATION IN POLARIZED MDCK CELLS

Lysosomal acid phosphatase (LAP) is synthesized as a type I membrane g lycoprotein and targeted to lysosomes via the plasma membrane. Its cyt oplasmic tail harbours a tyrosine-containing signal for rapid internal ization. Expression in Madine-Darby canine kidney cells results in dir ect sorting to the basolateral cell surface, rapid endocytosis and del ivery to lysosomes. In contrast, a deletion mutant lacking the cytopla smic tail is delivered to the apical plasma membrane where it accumula tes before it is slowly internalized. A chimeric protein, in which the cytoplasmic tail of LAP is fused to the extracytoplasmic and transmem brane domain of the apically sorted haemagglutinin, is sorted to the b asolateral plasma membrane. A series of truncation and substitution mu tants in the cytoplasmic tail was constructed and comparison of their polarized sorting and internalization revealed that the determinants f or basolateral sorting and rapid internalization reside in the same se gment of the cytoplasmic tail. The cytoplasmic factors decoding these signals, however, tolerate distinct mutations indicating that differen t receptors are involved in sorting at the trans-Golgi network and at the plasma membrane.