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 proteins have been identified, forming a family of proteins known as tyrosinase-related proteins. Two members of this family, tyrosinase and gp75, are well-characterized melanocyte differentiation antigens. Our previous studies have shown that gp75, the mouse brown locus protein, is sorted to melanosomes along the endocytic pathway, directed by a hexapeptide 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 cells. Cell surface expression of gp75 was also detected, representing 2% of cellular gp75. Characterization of secretory gp75 cells showed that 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 glycosylated than endocytic/melanosomal gp75, containing trans-Golgi processed sugar residues; and (iii) generated post-translationally in an acid sensitive compartment after processing in the trans-Golgi, and secreted rapidly after generation. Thus, these endocytic/melanosomal membrane proteins can be processed to abundant secretory forms, probably in an endocytic compartment through a potentially novel secretory pathway.
Xu
Y
Y
Memorial Sloan-Kettering Cancer Center and Cornell University Graduate School of Medical Sciences, New York, NY 10021, USA.
Setaluri
V
V
Takechi
Y
Y
Houghton
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AN
D000818:Animals; D005347:Fibroblasts / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011506:Proteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase