title: Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin.
abstract: 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.
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Srijana
authors.initials: S
authors.lastname: Upadhyay
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Xinping
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: David
authors.initials: D
authors.lastname: Lowry
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Jackson
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Roberson
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843, USA. Electronic address: xlin@bio.tamu.edu.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Lin
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000378:metabolism*; D001233:Aspergillus nidulans / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis; D005656:Fungal Proteins / Q000096:biosynthesis*; D008543:Melanins / Q000096:biosynthesis*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D016296:Mutagenesis; D048630:Polyketide Synthases / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D048948:14-3-3 Proteins; D005656:Fungal Proteins; D008543:Melanins; D020033:Protein Isoforms; D058305:Sorting Nexins; D000090802:rab7 GTP-Binding Proteins; D048630:Polyketide Synthases; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins