MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes.
More than 125 genes that regulate pigmentation have been identified to date. Of those, MART-1 has been widely studied as a melanoma-specific antigen and as a melanosome-specific marker. Whereas the functions of other melanosomal proteins, such as tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, and Pmel17, are known, the function of MART-1 in melanogenesis, is unclear. A role for MART-1 in pigmentation is expected because its expression pattern and subcellular distribution is quite similar to the other melanosomal proteins and usually correlates with melanin content. We investigated the function of MART-1 using a multidisciplinary approach, including the use of siRNA to inhibit MART-1 function and the use of transfection to re-express MART-1 in MART-1-negative cells. We show that MART-1 forms a complex with Pmel17 and affects its expression, stability, trafficking, and the processing which is required for melanosome structure and maturation. We conclude that MART-1 is indispensable for Pmel17 function and thus plays an important role in regulating mammalian pigmentation.
Hoashi
Toshihiko
T
Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Watabe
Hidenori
H
Muller
Jacqueline
J
Yamaguchi
Yuji
Y
Vieira
Wilfred D
WD
Hearing
Vincent J
VJ
D000818:Animals; D000951:Antigens, Neoplasm; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D058965:MART-1 Antigen; D008545:Melanoma / Q000378:metabolism; D020460:Melanosomes / Q000502:physiology* / Q000648:ultrastructure; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010858:Pigmentation / Q000502:physiology; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D058951:gp100 Melanoma Antigen