Siamese cat tyrosinase has enhanced proteasome degradation and increased cellular aggregation

Abstract

AbstractSiamese cats are a notable example of a temperature-sensitive partial albinism phenotype. The signature color-pointing pattern is the result of an amino acid substitution – G302R – in the cysteine-rich domain of feline tyrosinase. The precise mechanism for the loss of tyrosinase enzyme activity due to this mutation is unknown.ObjectiveWe have used a cellular biology approach to begin unravel relationships between feline coloration, behavior and increased risk for feline cognitive dysfunction syndrome. GFP-fusion constructs of wild type domestic short hair tyrosinase and Siamese (G302R) tyrosinase generated to study cellular trafficking, degradation and the propensity for cellular aggregation.Data DescriptionC-terminal GFP G302R expression has reduced Golgi localization, increased cytosolic fractions with reduced calnexin co-localization. N-terminal GFP constructs were retained in the ER, with little to no Golgi associated forms. C-terminal and N-terminal GFP G302R TYR is observed to have increased high molecular weight aggregation following proteasome inhibition.