Pmel17 initiates premelanosome morphogenesis within multivesicular bodies

Melanosomes are tissue-specific organelles within which melanin is synthesi zed and stored. The melanocyte-specific glycoprotein Pmel17 is enriched in the lumen of premelanosomes, where it associates with characteristic striat ions of unknown composition upon which melanin is deposited. However, Pmel1 7 is synthesized as an integral membrane protein. To clarify its physical l inkage to premelanosomes, we analyzed the posttranslational processing of h uman Pmel17 in pigmented and transfected nonpigmented cells. We show that P mel17 is cleaved in a post-Golgi compartment into two disulfide-linked subu nits: a large lumenal subunit, Ma, and an integral membrane subunit, Mp. Th e two subunits remain associated intracellularly, indicating that detectabl e Ma remains membrane bound. We have previously shown that Pmel17 accumulat es on intralumenal membrane vesicles and striations of premelanosomes in pi gmented cells. In transfected nonpigmented cells Pmel17 associates with the intralumenal membrane vesicles of multivesicular bodies; cells overexpress ing Pmel17 also display structures resembling premelanosomal striations wit hin these compartments. These results suggest that Pmel17 is sufficient to drive the formation of striations from within multivesicular bodies and is thus directly involved in the biogenesis of premelanosomes.