Phenotypic reversal of the btn1 defects in yeast by chloroquine: A yeast model for Batten disease
AUTOR(ES)
Pearce, David A.
FONTE
The National Academy of Sciences
RESUMO
BTN1 of Saccharomyces cerevisiae encodes an ortholog of CLN3, the human Batten disease gene. We have reported previously that deletion of BTN1, btn1-Δ, resulted in a pH-dependent resistance to d-(−)-threo-2-amino-1-[p-nitrophenyl]-1,3-propanediol (ANP). This phenotype was caused by btn1-Δ 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-Δ 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-Δ strains continue to grow. This phenotypic reversal of btn1-Δ can be considered for developing a therapy for Batten disease.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18035Documentos Relacionados
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