MISROUTING OF TYROSINASE WITH A TRUNCATED CYTOPLASMIC TAIL AS A RESULT OF THE MURINE PLATINUM (C(P)) MUTATION

Mice homozygous for the platinum (c(p)) allele at the albino locus man ifest severe oculocutaneous albinism despite the presence in vitro of tyrosinase activity at 25% wild-type levels. We demonstrate that the c (p) allele results from an A --> T substitution, changing a lysine res idue at position 489 to a termination codon, with truncation of tyrosi nase's cytoplasmic tail. In choroidal melanocytes of neonatal mutant m ice, tyrosinase activity could be detected in the trans Golgi network, but was absent from melanosomes. Instead, it was detected in vesicles in the cell periphery and dendrites, and on the extracellular surface . In the retinal pigment epithelium, activity was present on the extra cellular apical and basolateral surfaces. Our results demonstrate misr outing of a mutant tyrosinase lacking its cytoplasmic tail. providing an explanation for the severe effect of this mutation on ocular and cu taneous pigmentation. (C) Academic Press Limited