Cysteine transport in melanosomes from murine melanocytes
Cysteine transport in melanosomes from murine melanocytes
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DOI：
10.1111/j.1600-0749.1999.tb00502.x
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发表时间：
1999-02-01
期刊：
影响因子：
--
通讯作者：
Hearing, VJ
中科院分区：
文献类型：
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作者：
Potterf, SB;Virador, V;Hearing, VJ
褐黑素的合成需要在哺乳动物黑素生成过程中掺入含硫醇的化合物。由于黑色素仅在专门的膜结合细胞器（称为黑素体）中产生，因此此类硫醇供体必须穿过从细胞质到黑素体内部的膜屏障，因此半胱氨酸和/或谷胱甘肽（GSH）被认为是合适的硫醇供体，尽管以前没有表征这些化合物进入黑素体的特征。在这项研究中，我们表明半胱氨酸以温度和浓度依赖性方式转运，在反转运实验中获得了额外的证据，证明半胱氨酸摄取是由载体介导的过程产生的，而不是由于简单的扩散或膜通道所致，其中预载有半胱氨酸甲基化物的黑素体比未加载的对照摄取显着更多的[S-35]半胱氨酸。相反，我们无法在很宽的浓度范围内检测到[S-35]GSH的任何显着摄取，在无论是否存在还原剂，这项研究首次证明了半胱氨酸的黑素体膜转运，并且强烈表明游离半胱氨酸是哺乳动物黑素细胞中用于合成褐黑素的硫醇来源。
The synthesis of pheomelanin requires the incorporation of thiol-containing compound(s) during the process of mammalian melanogenesis. Since melanins are produced only in specialized, membrane-bound organelles, known as melanosomes, such thiol donor(s) must cross the membrane barrier from the cytosol to the melanosome interior, Cysteine and/or glutathione (GSH) were proposed as suitable thiol donors, although uptake of these compounds into melanosomes was not previously characterized, In this study, we show that cysteine is transported, in a temperature- and concentration-dependent manner, across membranes of melanosomes derived from murine melanocytes, Additional proof that cysteine uptake results from a carrier-mediated process and is not due to simple diffusion or to a membrane channel, was obtained in countertransport experiments, in which melanosomes preloaded with cysteine methyl eater took up significantly more [S-35]cysteine than did unloaded controls, In contrast, we were unable to detect any significant uptake of [S-35]GSH over a wide concentration range, in the presence or in the absence of reducing agent, This study is the first demonstration of melanosomal membrane transport of cysteine, and it strongly suggests that free cysteine is the thiol source utilized for pheomelanin synthesis in mammalian melanocytes.