title: Yeast ARL1 encodes a regulator of K+ influx.
abstract: A molecular genetic approach was undertaken in Saccharomyces cerevisiae to examine the functions of ARL1, encoding a G protein of the Ras superfamily. We show here that ARL1 is an important component of the control of intracellular K(+). The arl1 mutant was sensitive to toxic cations, including hygromycin B and other aminoglycoside antibiotics, tetramethylammonium ions, methylammonium ions and protons. The hygromycin-B-sensitive phenotype was suppressed by the inclusion of K(+) and complemented by wild-type ARL1 and an allele of ARL1 predicted to be unbound to nucleotide in vivo. The arl1 mutant strain internalized approximately 25% more [(14)C]-methylammonium ion than did the wild type, consistent with hyperpolarization of the plasma membrane. The arl1 strain took up 30-40% less (86)Rb(+) than did the wild type, showing an inability to regulate K(+) import properly, contributing to membrane hyperpolarity. By contrast, K(+) and H(+) efflux were undisturbed. The loss of ARL1 had no effect on the steady-state level or the localization of a tagged version of Trk1p. High copy suppressors of the hygromycin-B phenotype included SAP155, encoding a protein that interacts with the cell cycle regulator Sit4p, and HAL4 and HAL5, encoding Ser/Thr kinases that regulate the K(+)-influx mediators Trk1p and Trk2p. These results are consistent with a model in which ARL1, via regulation of HAL4/HAL5, governs K(+) homeostasis in cells.
authors.affiliation: Department of Biology, 406 Reiss Science Center, Box 571229, Georgetown University, Washington, DC 20057, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Munson
authors.forename: Devon H
authors.initials: DH
authors.lastname: Haydon
authors.forename: Sherie L
authors.initials: SL
authors.lastname: Love
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Fell
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Palanivel
authors.forename: Anne G
authors.initials: AG
authors.lastname: Rosenwald
mesh_terms: D000483:Alleles; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D018628:Gene Dosage; D005816:Genetic Complementation Test; D006706:Homeostasis; D006921:Hygromycin B / Q000494:pharmacology; D008744:Methylamines / Q000378:metabolism / Q000494:pharmacology; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011188:Potassium / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011522:Protons; D012413:Rubidium / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D002412:Cations; D008744:Methylamines; D011522:Protons; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C068664:TRK1 protein, S cerevisiae; D006921:Hygromycin B; C027451:methylamine; D017346:Protein Serine-Threonine Kinases; C487039:ARL1 protein, S cerevisiae; D020559:Monomeric GTP-Binding Proteins; D012413:Rubidium; D011188:Potassium