Functional Coupling between the Unfolded Protein Response and Endoplasmic Reticulum/Golgi Ca <sup>2+</sup> -ATPases Promotes Stress Tolerance, Cell Wall Biosynthesis, and Virulence of Aspergillus fumigatus
Martin Weichert, José P. Guirao-Abad, Vishukumar Aimanianda, Karthik Krishnan, Christina Grisham, Patrick Snyder, Alex Sheehan, Ruthvik R. Abbu, Hong Liu, Scott G. Filler, Eric Gruenstein, Jean‐Paul Latgé, David S. Askew
Abstract
The UPR is an intracellular signal transduction pathway that maintains homeostasis of the ER. The pathway is also tightly linked to the expression of virulence-related traits in diverse species of human-pathogenic and plant-pathogenic fungal species, including the predominant mold pathogen infecting humans, Aspergillus fumigatus . Despite advances in the understanding of UPR signaling, the linkages and networks that are governed by this pathway are not well defined. In this study, we revealed that the UPR is a major driving force for stimulating Ca 2+ influx at the ER and Golgi membranes and that the coupling between the UPR and Ca 2+ import is important for virulence, cell wall biosynthesis, and resistance to antifungal compounds that inhibit Ca 2+ signaling.