title: Protein kinase A signaling and calcium ions are major players in PAF mediated toxicity against Aspergillus niger.
abstract: The Penicillium chrysogenum antifungal protein PAF is toxic against potentially pathogenic Ascomycetes. We used the highly sensitive aequorin-expressing model Aspergillus niger to identify a defined change in cytoplasmic free Ca(2+) dynamics in response to PAF. This Ca(2+) signature depended on an intact positively charged lysine-rich PAF motif. By combining Ca(2+) measurements in A. niger mutants with deregulated cAMP/protein kinase A (PKA) signaling, we proved the interconnection of Ca(2+) perturbation and cAMP/PKA signaling in the mechanistic function of PAF. A deep understanding of the mode of action of PAF is an invaluable prerequisite for its future application as new antifungal drug.
authors.affiliation: Biocenter, Division of Molecular Biology, Medical University of Innsbruck, Innrain 80, A-6020 Innsbruck, Austria; Division of Hygiene and Medical Microbiology, Schöpfstrasse 41, Medical University of Innsbruck, A-6020 Innsbruck, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Binder
authors.affiliation: Department of Biotechnology, National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Benčina
authors.affiliation: Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Fizil
authors.affiliation: Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Batta
authors.affiliation: Biocenter, Division of Molecular Biology, Medical University of Innsbruck, Innrain 80, A-6020 Innsbruck, Austria; Centre for Biotechnology, Maharshi Dayanand University, IN-124001 Rohtak, Haryana, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chhillar
authors.affiliation: Biocenter, Division of Molecular Biology, Medical University of Innsbruck, Innrain 80, A-6020 Innsbruck, Austria. Electronic address: florentine.marx@i-med.ac.at.
authors.forename: Florentine
authors.initials: F
authors.lastname: Marx
mesh_terms: D020816:Amino Acid Motifs; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001234:Aspergillus niger / Q000201:enzymology*; D020013:Calcium Signaling / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; C097832:PAF protein, Penicillium chrysogenum; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Antifungal protein; Aspergillus niger; Calcium homeostasis; PAF; Protein kinase A signaling