ABCB6 Regulates The Trafficking Of TYRP1

Melanosome is considered as a classic member of the well-documented family of lysosome-related organelles(LROs).As the specialized organelle to produce melanin,the development and maturation of melanosomes are closely related with the color of human skin,hair and eyes.ABCB6 belongs to the superfamily of ATP-binding cassette transport proteins,while mutations in ABCB6 gene may result in several diseases.Our previous study has discovered that mutation in ABCB6 gene is responsible for dyschromatosis universalis hereditaria(DUH).However,its underlying mechanism of mutant ABCB6 causing DUH is still poorly understood.In this study,recombinant plasmids of wild type and mutant type mouse ABCB6-EGFP fusion protein had successfully constructed.Wild type and mutant type human ABCB6 expression vectors constructed previously were also used at the same time.Our results showed that ABCB6 involved in the trafficking of TYRP1 in MNT-1 or B16F1 cells through laser scan confocal microscope observing its subcellular localization and western blot assays detecting the expression of TYRP1.Mutant ABCB6 caused retention of TYRP1 in the trans-golgi network(TGN)and these mislocalized TYRP1 would be degraded by lysosome.The similar phenotypes in cells was showed in the melanocytes which ABCB6 was knockdown by RNA interference technology.TYRP1 signal in these B16F1 cells was partially rescued when they were treated with lysosome inhibitor.All of these findings demonstrated that ABCB6 in melanocyte played important role in melanin metabolism through regulating the trafficking of TYRP1.It illuminates preliminarily the pathogenesis of DUH and provides us an useful clue for further study on the TYRP1 trafficking in melanocyte.