ABSTRACT
Prion conversion from a soluble protein to an aggregated state may be involved in the cellular adaptation of yeast to the environment. However, it remains unclear whether and how cells actively use prion conversion to acquire a fitness advantage in response to environmental stress. We identified Mod5, a yeast transfer RNA isopentenyltransferase lacking glutamine/asparagine-rich domains, as a yeast prion protein and found that its prion conversion in yeast regulated the sterol biosynthetic pathway for acquired cellular resistance against antifungal agents. Furthermore, selective pressure by antifungal drugs on yeast facilitated the de novo appearance of Mod5 prion states for cell survival. Thus, phenotypic changes caused by active prion conversion under environmental selection may contribute to cellular adaptation in living organisms.
Subject(s)
Alkyl and Aryl Transferases/chemistry , Alkyl and Aryl Transferases/metabolism , Antifungal Agents/pharmacology , Prions/chemistry , Saccharomyces cerevisiae Proteins/chemistry , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/physiology , Stress, Physiological , Alkyl and Aryl Transferases/genetics , Biosynthetic Pathways , Crosses, Genetic , Drug Resistance, Fungal , Ergosterol/biosynthesis , Fluorouracil/pharmacology , Microbial Viability , Prions/genetics , Prions/metabolism , Protein Conformation , Protein Structure, Tertiary , RNA, Fungal/metabolism , RNA, Transfer/metabolism , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolism , Saccharomyces cerevisiae/chemistry , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics , Selection, Genetic , SolubilityABSTRACT
Adult neocortex contains dividing satellite glia population even though their characteristics and functions have still remained unknown. Nestin(+)/NG2(+) cells as major fraction of dividing glial cells express bicuculline-sensitive gamma-aminobutyric acid A (GABA(A)) receptors and receive GABAergic inputs. Due to their high [Cl(-)](i), GABAergic activation depolarized the cells and then induced Ca(2+) influx into them. To assess an effect of this GABAergic excitation, we looked for the expression of neurotrophic factors. Among them, we detected the expression of brain-derived neurotrophic factor (BDNF) on the cells. The level of BDNF expression was elevated after cortical ischemia, and this elevation was blocked by bumetanide, an inhibitor for NKCC1 that blocks the GABAergic depolarization. Furthermore, performing a modified adhesive removal test, we observed that the treatment of bumetanide significantly attenuated the recovery in somatosensory dysfunction. Our results may shed a light on satellite glia population in the cortex and imply their roles in the functional recovery after ischemic injuries.
