The melanosome: The perfect model for cellular responses to the environment
The melanosome: The perfect model for cellular responses to the environment
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DOI：
10.1034/j.1600-0749.13.s8.7.x
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发表时间：
2000-01-01
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影响因子：
--
通讯作者：
Hearing, VJ
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文献类型：
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作者：
Hearing, VJ
黑素细胞在哺乳动物中起着关键作用，包括调节皮肤、毛发和眼睛的固有色素沉着，参与胚胎发育以及抵御电离辐射的光保护作用。色素本身，可能由于其前体固有的细胞毒性特性，在被称为黑素体的膜结合细胞器内合成并沉积。然而，黑素体的结构以及它们的特性差异很大，从相对无序、色素沉着不良的褐黑素体到高度结构化、黑色素化的真黑素体不等。黑素细胞通过高度复杂的细胞内信号传导机制对各种生理刺激作出反应，例如黑素细胞刺激素（MSH）、刺鼠信号蛋白（ASP）、内皮素和/或紫外线（UVL），这些机制可引起黑素体和黑素细胞形态的显著变化。MSH和UVL刺激黑素生成基因的转录，导致产生的真黑素量大幅增加，而ASP作为MSH的拮抗剂，抑制这些相同基因的转录。最近的研究表明，黑素细胞特异性转录因子，如MITF，在这些反应中起重要作用，但普遍存在的转录因子，如ITF2和E2A，也参与其中。几乎所有已知的细胞内信号通路都会影响色素沉着的一个或多个参数，很明显，黑素细胞特异性过程和基本的细胞维持过程都会受到这种调节的影响。黑素的特性，包括其光保护功能，可能会通过这种刺激反应得到优化。旨在阐明所涉及的调节机制和由此产生的功能变化的研究表明，黑素体是研究此类生物反应机制的理想模型。
Melanocytes play critical roles in mammals, including the regulation of constitutive pigmentation in the skin, hair, and eyes, in embryological development, and in photoprotection from ionizing radiation. The pigments themselves, possibly due to the inherent cytotoxic properties of their precursors, are synthesized and deposited within membrane-bound organelles known as melanosomes, However, the structure of melanosomes, and thus their characteristic properties, varies widely, from relatively disorganized, poorly pigmented pheomelanosomes to highly structured, melanized eumelanosomes. Melanocytes respond to various physiological stimuli, such as melanocyte-stimulating hormone (MSH), agouti signal protein (ASP), endothelins and/or ultra violet light (UVL) by highly complex intracellular signaling mechanisms that can elicit dramatic changes in melanosome and melanocyte morphology. MSH and UVL stimulate transcription of melanogenic genes that elicit dramatic increases in the amount of eumelanins produced, whereas ASP serves as an antagonist of MSH and inhibits the transcription of those same genes. Recent studies have shown that melanocyte-specific transcription factors, such as MITF, play important roles in these responses, but ubiquitous transcription factors, such as ITF2 and E2A, are also involved. Virtually all known intracellular signaling pathways affect one or more parameters of pigmentation, and it is clear that both melanocyte-specific and basic housekeeping processes are affected by such modulation. The properties of melanins, including their photoprotective function, may be optimized by such stimulatory responses. Studies targeted at elucidating the regulatory mechanisms involved and the functional changes that result demonstrate that the melanosome is the perfect model to study such biological response mechanisms.