SORTING AND SECRETION OF A MELANOSOME MEMBRANE-PROTEIN, GP75 TRP1/

The melanosome is an organelle specialized for melanin synthesis that is derived from the endocytic pathway, Several melanosome membrane pro teins have been identified, forming a family of proteins known as tyro sinase-related proteins, Two members of this family, tyrosinase and gp 75, are well-characterized melanocyte differentiation antigens, Our pr evious studies have shown that gp75, the mouse brown locus protein, is sorted to melanosomes along the endocytic pathway, directed by a hexa peptide sorting signal located in the cytoplasmic tail. In this study, we report the unexpected finding that a portion of gp75 is secreted, Substantial levels of secretory, gp75 were detected in melanocytic cel ls, Cell surface expression of gp75 was also detected, representing 2% of cellular gp75, Characterization of secretory gp75 sells showed tha t it is: (i) a truncated form that lacks the transmembrane region, the cytoplasmic tail where the endosomal sorting signal is located, and a small portion of the lumenal domain; (ii) more extensively glycosylat ed than endocytic/melanosomal gp75, containing trans-Golgi processed s ugar residues; and (iii) generated post-translationally in an acid sen sitive compartment after processing in the trans-Golgi, and secreted r apidly after generation, Thus, these endocytic/melanosomal membrane pr oteins can be processed to abundant secretory forms, probably in an en docytic compartment through a potentially novel secretory pathway.