Summary

Tyrosinase is a type I membrane protein found in melanosomes, which are lysosomal-like organelles and specific for pigment cells. A mutation of mouse tyrosinase, platinum (cp), leads to truncation of tyrosinase's cytosolic tail, and results in misrouting to the cell periphery. In this study, we expressed chimeras of wild-type and mutant cytosolic tails of mouse tyrosinase fused to rat lysosome-associated membrane protein-1 luminal and transmembrane domain to study sorting of tyrosinase in Madin-Darby canine kidney cells. The study shows that the mouse tyrosinase cytosolic tail is necessary and sufficient to mediate sorting of a heterologous type I membrane protein to compartments of the lysosomal lineage. Whereas deletions of 7 or 10 C-terminal amino acids of the tail still result in sorting to lysosomes, a deletion mutant corresponding to platinum (cp) tail fails to sort correctly and corroborates the in situ findings in cp homozygous mutant mice. Correct sorting of tyrosinase-lysosome-associated membrane protein-1 chimeras is mediated by the interplay of a di-leucine signal and a tyrosine motif of the Y-X-X-O type.