Tyrosine transport into melanosomes is increased following stimulation of melanocyte differentiation.
A variety of physiological factors can stimulate differentiation of melanocytes to increase pigmentation, and critical to this process is the transport of the melanogenic substrate (tyrosine) into melanosomes. In this study, we examined whether stimulation of melanogenesis affects melanosomal tyrosine transport. Tyrosine uptake increased almost 2-fold in melanosomes derived from melanocytes treated with melanocyte-stimulating hormone (MSH), which acts to increase intracellular cAMP levels, resulting in the up-regulation of many genes involved in melanogenesis. Stimulation of melanoma cells with dibutyryl cAMP increased melanosomal tyrosine transport 2- to 3-fold after 24 to 48 hrs, with peak levels occurring after 3 to 5 days of treatment, suggesting that de novo gene expression may be required. The cAMP-induced increase in melanosomal tyrosine transport could be effectively competed with phenylalanine or tryptophan, but not with dopamine or proline, suggesting either that a pool of transporters with greater tyrosine transporting ability pre-exists, or that a greater number of tyrosine transporters reside within the melanosomal membrane. These results illustrate a rare example of hormonal plasma membrane stimulation which transduces a signal for increased vesicular transport of an amino acid.
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
S B
SB
Potterf
V J
VJ
Hearing
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D007700:Kinetics; D007980:Levodopa / Q000494:pharmacology; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D000596:Amino Acids; D014443:Tyrosine; D007980:Levodopa; D003994:Bucladesine; D009074:Melanocyte-Stimulating Hormones