Subunit C of V-ATPase-VmaC Is Required for Hyphal Growth and Conidiation in A. fumigatus by Affecting Vacuolar Calcium Homeostasis and Cell Wall Integration.

Aspergillus fumigatus is a widespread airborne fungal pathogen in humans. However, the functional genes in A. fumigatus that may contribute to its pathogenesis have not yet been fully identified. Vacuolar H + -ATPase is universal in eukaryotic organisms but exhibits specific roles in various species. Here, we identified VmaC as a putative subunit of vacuolar H + -ATPase in A. fumigatus that is widely conserved through evolution. The C-terminal hydrophobic domain of VmaC plays a critical role in its vacuolar localization and growth and conidiation. Deletion or turn-off of VmaC encoding gene- AfvmaC expression is not lethal but leads to a very sick and tiny colony phenotype, which is different from that of yeast with conditional ScvmaC defects. Furthermore, we found that AfvmaC not only participates in maintaining calcium homeostasis and vacuolar acidity but is also involved in cell wall integration pathway regulation, highlighting the importance of the vacuole as a storage organelle associated with many aspects of cellular homeostasis. This study indicates that fungal VmaC is relatively conserved. When compared to that in model yeasts, VmaC in A. fumigatus is required for hyphal growth and conidiation, suggesting that specific motifs in VmaC might be functioned in Aspergilli .