title: A second component of the SltA-dependent cation tolerance pathway in Aspergillus nidulans.
abstract: The transcriptional response to alkali metal cation stress is mediated by the zinc finger transcription factor SltA in Aspergillus nidulans and probably in other fungi of the pezizomycotina subphylum. A second component of this pathway has been identified and characterized. SltB is a 1272 amino acid protein with at least two putative functional domains, a pseudo-kinase and a serine-endoprotease, involved in signaling to the transcription factor SltA. Absence of SltB activity results in nearly identical phenotypes to those observed for a null sltA mutant. Hypersensitivity to a variety of monovalent and divalent cations, and to medium alkalinization are among the phenotypes exhibited by a null sltB mutant. Calcium homeostasis is an exception and this cation improves growth of sltΔ mutants. Moreover, loss of kinase HalA in conjunction with loss-of-function sltA or sltB mutations leads to pronounced calcium auxotrophy. sltA sltB double null mutants display a cation stress sensitive phenotype indistinguishable from that of single slt mutants showing the close functional relationship between these two proteins. This functional relationship is reinforced by the fact that numerous mutations in both slt loci can be isolated as suppressors of poor colonial growth resulting from certain null vps (vacuolar protein sorting) mutations. In addition to allowing identification of sltB, our sltB missense mutations enabled prediction of functional regions in the SltB protein. Although the relationship between the Slt and Vps pathways remains enigmatic, absence of SltB, like that of SltA, leads to vacuolar hypertrophy. Importantly, the phenotypes of selected sltA and sltB mutations demonstrate that suppression of null vps mutations is not dependent on the inability to tolerate cation stress. Thus a specific role for both SltA and SltB in the VPS pathway seems likely. Finally, it is noteworthy that SltA and SltB have a similar, limited phylogenetic distribution, being restricted to the pezizomycotina subphylum. The relevance of the Slt regulatory pathway to cell structure, intracellular trafficking and cation homeostasis and its restricted phylogenetic distribution makes this pathway of general interest for future investigation and as a source of targets for antifungal drugs.
authors.affiliation: Departamento de Biología Celular y Molecular, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Mellado
authors.affiliation: Section of Microbiology, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Calcagno-Pizarelli
authors.affiliation: Department of Genetics and Evolution, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Lockington
authors.affiliation: Dept. of Applied Chemistry, Faculty of Chemistry, University of the Basque Country, Manuel de Lardizabal, 3, 20018 San Sebastian, Spain.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Cortese
authors.affiliation: Department of Genetics and Evolution, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Kelly
authors.affiliation: Departamento de Biología Celular y Molecular, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain; Section of Microbiology, Imperial College London, Flowers Building, Armstrong Road, London SW7 2AZ, UK.
authors.forename: Herbert N
authors.initials: HN
authors.lastname: Arst
authors.affiliation: Departamento de Biología Celular y Molecular, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain. Electronic address: eespeso@cib.csic.es.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Espeso
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000235:genetics* / Q000378:metabolism*; D002412:Cations / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D056426:Genetic Loci; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D016415:Sequence Alignment; D015398:Signal Transduction; D014157:Transcription Factors; D016335:Zinc Fingers
chemical_list: D002412:Cations; D005656:Fungal Proteins; D014157:Transcription Factors
keywords: Cation-stress response; Mutation; Signaling pathway; Suppressor; Vacuolar protein sorting; pH regulation