The tyrosinase tail mediates sorting to the lysosomal compartment in MDCK cells via a di-leucine and a tyrosine-based signal

Tyrosinase is a type I membrane protein found in melanosomes, which are lys osomal-like organelles and specific for pigment cells, A mutation of mouse tyrosinase, platinum (c(p)), leads to truncation of tyrosinase's cytosolic tail, and results in misrouting to the cell periphery, In this study, we ex pressed chimeras of wild-type and mutant cytosolic tails of mouse tyrosinas e fused to rat lysosome-associated membrane protein-1 luminal and transmemb rane domain to study sorting of tyrosinase in Madin-Darby canine kidney cel ls, The study shows that the mouse tyrosinase cytosolic tail is necessary a nd sufficient to mediate sorting of a heterologous type I membrane protein to compartments of the lysosomal lineage, Whereas deletions of 7 or 10 C-te rminal amino acids of the tail still result in sorting to lysosomes, a dele tion mutant corresponding to platinum (c(p)) tail fails to sort correctly a nd corroborates the in situ findings in c(p) homozygous mutant mice. Correc t sorting of tyrosinase-lysosome-associated membrane protein-1 chimeras is mediated by the interplay of a di-leucine signal and a tyrosine motif of th e Y-X-X-empty set type.