title: A conserved C-terminal domain of the Aspergillus fumigatus developmental regulator MedA is required for nuclear localization, adhesion and virulence.
abstract: MedA is a developmental regulator that is conserved in the genome of most filamentous fungi. In the pathogenic fungus Aspergillus fumigatus MedA regulates conidiogenesis, adherence to host cells, and pathogenicity. The mechanism by which MedA governs these phenotypes remains unknown. Although the nuclear import of MedA orthologues has been reported in other fungi, no nuclear localization signal, DNA-binding domain or other conserved motifs have been identified within MedA. In this work, we performed a deletion analysis of MedA and identified a novel domain within the C-terminal region of the protein, designated MedA(346-557), that is necessary and sufficient for nuclear localization of MedA. We further demonstrate that MedA nuclear localization is required for the function of MedA. Surprisingly, expression of the minimal nuclear localization fragment MedA(346-557) alone was sufficient to restore conidogenesis, biofilm formation and virulence to the medA mutant strain. Collectively these results suggest that MedA functions in the regulation of transcription, and that the MedA(346-557) domain is both necessary and sufficient to mediate MedA function.
authors.affiliation: Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
authors.forename: Qusai
authors.initials: Q
authors.lastname: Al Abdallah
authors.forename: Se-In
authors.initials: SI
authors.lastname: Choe
authors.forename: Paolo
authors.initials: P
authors.lastname: Campoli
authors.forename: Stefanie
authors.initials: S
authors.lastname: Baptista
authors.forename: Fabrice N
authors.initials: FN
authors.lastname: Gravelat
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Lee
authors.forename: Donald C
authors.initials: DC
authors.lastname: Sheppard
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000595:Amino Acid Sequence; D001232:Aspergillus fumigatus / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D018441:Biofilms / Q000254:growth & development*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D013172:Spores, Fungal / Q000235:genetics / Q000254:growth & development; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D014157:Transcription Factors