Diverse roles of conserved asparagine-linked glycan sites on tyrosinase family glycoproteins

The tyrosinase family of genes has been conserved throughout vertebrate evo lution. The role of conserved N-glycan sites in sorting, stability, and act ivity of tyrosinase family proteins was investigated using two family membe rs from two different species, mouse gp75/tyrosinase-related protein (TRP)- 1/Tyrp1 and human tyrosinase. Potential N-linked glycosylation sites on the lumenal domains of mouse gp75/TRP-1/Tyrp1 and human tyrosinase were elimin ated by site-directed mutagenesis (Asn to Gln substitutions). Our results s how that selected conserved N-glycan sites on tyrosinase family members are crucial for stability in the secretory pathway and endocytic compartment a nd for enzymatic activity, Different glycan sites on the same tyrosinase fa mily polypeptide can perform distinct functions, and conserved sites on tyr osinase family paralogues can perform different functions. (C) 2001 Academi c Press.