The @entity2118 melanin is produced in melanocytes in highly specialized organelles known as melanosomes. Melanosomes are related to the organelles of the endosomal/lysosomal pathway and can have a low internal pH. In the present study we have shown that melanin synthesis in @entity1 pigment cell lysates is maximal at pH 6.8. We therefore investigated the role of intramelanosomal pH as a possible control mechanism for melanogenesis. To do this we examined the effect of neutralizing melanosomal pH on @entity11442 activity and melanogenesis in 11 @entity1 melanocyte cultures and in 3 @entity320 lines. All melanocyte cultures (9 of 9) from Caucasian skin as well as two @entity320 cell lines with comparable melanogenic activity showed rapid (within 24 h) increases in melanogenesis in response to neutralization of melanosomal pH. Chemical analysis of total melanin indicated a preferential increase in eumelanin production. Electron microscopy revealed an accumulation of melanin and increased maturation of melanosomes in response to pH neutralization. In summary, our findings show that: (i) near neutral melanosomal pH is optimal for @entity1 @entity11442 activity and melanogenesis; (ii) melanin production in Caucasian melanocytes is suppressed by low melanosomal pH; (iii) the ratio of eumelanin/phaeomelanin production and maturation rate of melanosomes can be regulated by melanosomal pH. We conclude that melanosomal pH is an essential factor which regulates multiple stages of melanin production. Furthermore, since we have recently identified that pink locus product ( @entity7826 ) mediates neutralization of melanosomal pH, we propose that @entity7826 is a key control point for skin pigmentation. We would further propose that the wide variations in both constitutive and facultative skin pigmentation seen in the @entity1 population could be associated with the high degree of P-locus polymorphism.

Melanosomal pH controls rate of melanogenesis, eumelanin/phaeomelanin ratio and melanosome maturation in melanocytes and XXXX cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity7826 :: ('4948', 'Gene') :: ['P protein'] @entity2118 :: ('MESH:D010859', 'Disease') :: ['skin pigment'] @entity11442 :: ('7299', 'Gene') :: ['tyrosinase'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma']
@entity320 :: (MESH:D008545,Disease) :: ['melanoma']
