Upadhyay Srijana, Xu Xinping, Lowry David, Jackson Jennifer C, Roberson Robert W, Lin Xiaorong
Department of Biology, Texas A&M University, College Station, TX 77843, USA.
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Cell Rep. 2016 Mar 22;14(11):2511-8. doi: 10.1016/j.celrep.2016.02.059. Epub 2016 Mar 10.
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.
黑色素的保护作用取决于其亚细胞定位。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位置和方式以及它如何作为细胞外颗粒沉积仍然不清楚。通过在病原体烟曲霉中进行正向遗传筛选，我们发现内体分选连接蛋白的突变消除了黑色素在细胞壁上的沉积。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传统分泌途径被募集到内体中。相比之下，晚期黑色素酶则积聚在细胞壁中。黑色素生物合成机制的这种亚细胞区室化在烟曲霉和构巢曲霉中均有发生。因此，真菌黑色素的生物合成似乎在内体中启动，通过胞吐作用导致黑色素在细胞外沉积，这与哺乳动物黑色素在源自内体的黑素小体中的合成和运输非常相似。
