Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin.
Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin.
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DOI：
10.1016/j.celrep.2016.02.059
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发表时间：
2016-03-22
期刊：
影响因子：
8.8
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Upadhyay S;Xu X;Lowry D;Jackson JC;Roberson RW;Lin X
黑色素的保护取决于其亚细胞位置。尽管大多数丝状真菌通过聚酮合酶途径合成黑色素，但黑色素生物合成发生的地点和方式，以及它如何沉积为细胞外颗粒，仍然难以捉摸。通过对病原体烟曲霉进行正向遗传筛选，我们发现内体分选连接蛋白的突变消除了黑色素细胞壁沉积。我们发现参与黑色素生物合成早期步骤的所有酶都通过非常规分泌途径被招募到内体中。相反，晚期黑色素酶积聚在细胞壁中。这种黑色素生物合成机制的亚细胞区室化发生在烟曲霉和构巢曲霉中。因此，真菌黑色素生物合成似乎是在内体中启动的，具有胞吐作用，导致黑色素细胞外沉积，非常类似于哺乳动物黑色素在内体衍生的黑素体中的合成和运输。
Protection by melanin depends on its subcellular location. Although most filamentous fungi synthesize melanin via a polyketide synthase pathway, where and how melanin biosynthesis occurs, and how it is deposited as extracellular granules, remain elusive. Using a forward genetic screen in the pathogen Aspergillus fumigatus, we find that mutations in an endosomal sorting nexin abolish melanin cell wall deposition. We find that all enzymes involved in the early steps of melanin biosynthesis are recruited to endosomes through a non-conventional secretory pathway. In contrast, late melanin enzymes accumulate in the cell wall. Such subcellular compartmentalization of the melanin biosynthetic machinery occurs in both A. fumigatus and A. nidulans. Thus, fungal melanin biosynthesis appears to be initiated in endosomes with exocytosis leading to melanin extracellular deposition, much like the synthesis and trafficking of mammalian melanin in endosomally-derived melanosomes.