THE CYTOPLASMIC TAIL OF THE MOUSE BROWN LOCUS PRODUCT DETERMINES INTRACELLULAR STABILITY AND EXPORT FROM THE ENDOPLASMIC-RETICULUM

Several melanosome membrane proteins have been identified, forming a f amily of proteins known as tyrosinase related proteins. Human TRP-1/gp 75 is sorted to melanosomes through the endoplasmic reticulum and Golg i complex to the endocytic pathway, directed by a sorting signal locat ed in the cytoplasmic tail, This hexapeptide cytoplasmic sequence, whi ch is conserved in the tyrosinase related protein family and through v ertebrate evolution, was shown to act also as a sorting signal in mous e gp75, confirming that its sorting and cellular retention function is conserved between human and mouse. The cytoplasmic tail influenced th e rate and efficiency of intracellular transport of gp75 from the endo plasmic reticulum to the cis-Golgi, Deletion of 33 or 27 amino acids f rom the carboxyl end of the 38 amino acid cytoplasmic tail of gp75 cau sed retention and rapid degradation of the truncated gp75 in the endop lasmic reticulum. This defective movement could be fully corrected by extending the truncated tail with the unrelated cytoplasmic tail of th e low density lipoprotein receptor, Thus, the cytoplasmic tail of mous e gp75 not only determines sorting to the endocytic/melanosomal compar tment, but also controls export from the endoplasmic reticulum to Golg i.