title: Phenotypic reversal of the btn1 defects in yeast by chloroquine: a yeast model for Batten disease.
abstract: BTN1 of Saccharomyces cerevisiae encodes an ortholog of CLN3, the human Batten disease gene. We have reported previously that deletion of BTN1, btn1-Delta, resulted in a pH-dependent resistance to D-(-)-threo-2-amino-1-[p-nitrophenyl]-1,3-propanediol (ANP). This phenotype was caused by btn1-Delta strains having an elevated ability to acidify growth medium through an elevated activity of the plasma membrane H(+)-ATPase, resulting from a decreased vacuolar pH during early growth. We have determined that growing btn1-Delta strains in the presence of chloroquine reverses the resistance to ANP, decreases the rate of medium acidification, decreases the activity of plasma membrane H(+)-ATPase, and elevates vacuolar pH. However, an additional effect of this phenotypic reversal is that activity of plasma membrane H(+)-ATPase is decreased further and vacuolar pH is increased further as btn1-Delta strains continue to grow. This phenotypic reversal of btn1-Delta can be considered for developing a therapy for Batten disease.
authors.affiliation: Department of Biochemistry, University of Rochester School of Medicine, Rochester, NY 14642, USA. david_pearce@urmc.rochester.edu
authors.forename: D A
authors.initials: DA
authors.lastname: Pearce
authors.forename: C J
authors.initials: CJ
authors.lastname: Carr
authors.forename: B
authors.initials: B
authors.lastname: Das
authors.forename: F
authors.initials: F
authors.lastname: Sherman
mesh_terms: D002738:Chloroquine / Q000494:pharmacology*; D016213:Cyclins; D005656:Fungal Proteins / Q000032:analysis / Q000235:genetics*; D050890:HSP30 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000032:analysis; D018832:Molecular Chaperones; D009472:Neuronal Ceroid-Lipofuscinoses / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014617:Vacuoles / Q000378:metabolism
chemical_list: C079895:CLN3 protein, S cerevisiae; C105199:CLN3 protein, human; D016213:Cyclins; D005656:Fungal Proteins; D050890:HSP30 Heat-Shock Proteins; C494390:HSP30 protein, S cerevisiae; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C489809:YHC3 protein, S cerevisiae; D002738:Chloroquine; D006180:Proton-Translocating ATPases