title: Arrestin-related proteins mediate pH signaling in fungi.
abstract: Metazoan arrestins bind to seven-transmembrane (7TM) receptors to regulate function. Aspergillus nidulans PalF, a protein involved in the fungal ambient pH signaling pathway, contains arrestin N-terminal and C-terminal domains and binds strongly to two different regions within the C-terminal cytoplasmic tail of the 7TM, putative pH sensor PalH. Upon exposure to alkaline ambient pH, PalF is phosphorylated and, like mammalian beta-arrestins, ubiquitinated in a signal-dependent and 7TM protein-dependent manner. Substitution in PalF of a highly conserved arrestin N-terminal domain Ser residue prevents PalF-PalH interaction and pH signaling in vivo. Thus, PalF is the first experimentally documented fungal arrestin-related protein, dispelling the notion that arrestins are restricted to animal proteomes. Epistasis analyses demonstrate that PalF posttranslational modification is partially dependent on the 4TM protein PalI but independent of the remaining pH signal transduction pathway proteins PalA, PalB, and PalC, yielding experimental evidence bearing on the order of participation of the six components of the pH signal transduction pathway. Our data strongly implicate PalH as an ambient pH sensor, possibly with the cooperation of PalI.
authors.affiliation: Departamento de Microbiología Molecular, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid 28040, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Herranz
authors.forename: José M
authors.initials: JM
authors.lastname: Rodríguez
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Bussink
authors.forename: Juan C
authors.initials: JC
authors.lastname: Sánchez-Ferrero
authors.forename: Herbert N
authors.initials: HN
authors.lastname: Arst
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Peñalva
authors.forename: Olivier
authors.initials: O
authors.lastname: Vincent
mesh_terms: D000595:Amino Acid Sequence; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D001233:Aspergillus nidulans / Q000235:genetics*; D004252:DNA Mutational Analysis; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000378:metabolism*; D005982:Glutathione Transferase; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D008969:Molecular Sequence Data; D010766:Phosphorylation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics*; D020798:Two-Hybrid System Techniques; D014452:Ubiquitins
chemical_list: D019390:Arrestins; D005656:Fungal Proteins; C107929:PALF protein, Emericella nidulans; C121840:PALH protein, Emericella nidulans; D043562:Receptors, G-Protein-Coupled; D014452:Ubiquitins; C450520:seven-transmembrane G-protein-coupled receptor; D005982:Glutathione Transferase