title: Misrouting of tyrosinase with a truncated cytoplasmic tail as a result of the murine platinum (cp) mutation.
abstract: Mice homozygous for the platinum (cp) allele at the albino locus manifest severe oculocutaneous albinism despite the presence in vitro of tyrosinase activity at 25% wild-type levels. We demonstrate that the cp allele results from an A-->T substitution, changing a lysine residue at position 489 to a termination codon, with truncation of tyrosinase's cytoplasmic tail. In choroidal melanocytes of neonatal mutant mice, 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 extracellular apical and basolateral surfaces. Our results demonstrate misrouting of a mutant tyrosinase lacking its cytoplasmic tail, providing an explanation for the severe effect of this mutation on ocular and cutaneous pigmentation.
authors.affiliation: Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Beermann
authors.forename: S J
authors.initials: SJ
authors.lastname: Orlow
authors.forename: R E
authors.initials: RE
authors.lastname: Boissy
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: Y L
authors.initials: YL
authors.lastname: Boissy
authors.forename: M L
authors.initials: ML
authors.lastname: Lamoreux
mesh_terms: D016115:Albinism, Oculocutaneous / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D002829:Choroid / Q000000981:diagnostic imaging; D004247:DNA / Q000032:analysis; D008544:Melanocytes / Q000000981:diagnostic imaging; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000201:enzymology*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014463:Ultrasonography
chemical_list: D008565:Membrane Proteins; D004247:DNA; D014442:Monophenol Monooxygenase