title: Aspergillus nidulans CkiA is an essential casein kinase I required for delivery of amino acid transporters to the plasma membrane.
abstract: Type I casein kinases are highly conserved among Eukaryotes. Of the two Aspergillus nidulans casein kinases I, CkiA is related to the δ/ε mammalian kinases and to Saccharomyces cerevisiae Hrr25p. CkiA is essential. Three recessive ckiA mutations leading to single residue substitutions, and downregulation using a repressible promoter, result in partial loss-of-function, which leads to a pleiotropic defect in amino acid utilization and resistance to toxic amino acid analogues. These phenotypes correlate with miss-routing of the YAT plasma membrane transporters AgtA (glutamate) and PrnB (proline) to the vacuole under conditions that, in the wild type, result in their delivery to the plasma membrane. Miss-routing to the vacuole and subsequent transporter degradation results in a major deficiency in the uptake of the corresponding amino acids that underlies the inability of the mutant strains to catabolize them. Our findings may have important implications for understanding how CkiA, Hrr25p and other fungal orthologues regulate the directionality of transport at the ER-Golgi interface.
authors.affiliation: Institut de Génétique et Microbiologie, Université Paris-Sud (XI), UMR 8621 CNRS 91450 Orsay, France.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Apostolaki
authors.forename: Laura
authors.initials: L
authors.lastname: Harispe
authors.forename: Ana María
authors.initials: AM
authors.lastname: Calcagno-Pizarelli
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vangelatos
authors.forename: Vicky
authors.initials: V
authors.lastname: Sophianopoulou
authors.forename: Herbert N
authors.initials: HN
authors.lastname: Arst
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Peñalva
authors.forename: Sotiris
authors.initials: S
authors.lastname: Amillis
authors.forename: Claudio
authors.initials: C
authors.lastname: Scazzocchio
mesh_terms: D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D001233:Aspergillus nidulans / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D047389:Casein Kinase I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008969:Molecular Sequence Data; D011392:Proline / Q000378:metabolism; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid
chemical_list: D026905:Amino Acid Transport Systems; D005656:Fungal Proteins; D018698:Glutamic Acid; D011392:Proline; D047389:Casein Kinase I