CELL BIOLOGY: Curing Disease in Yeast

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Science  07 Nov 2008:
Vol. 322, Issue 5903, pp. 825c
DOI: 10.1126/science.322.5903.825c

Batten disease is a neurodegenerative disorder linked to the pathological accumulation of material in lysosomes. In yeast the [URE3] phenotype is a prion (infectious protein) generated by the self-propagating amyloid form of the Ure2 protein, which regulates nitrogen catabolism. Yeast prions can arise and disappear spontaneously within populations, reflecting in part changes in the protein folding milieu. Kryndushkin et al. show that increased production of Btn2 protein or its homolog Cur1 can cure [URE3]. Conversely, deletion of BTN2 and CUR1 genes stabilizes the [URE3] phenotype. In cells expressing a fluorescently tagged version of Btn2p, fluorescence accumulated at a single point close to the nucleus and vacuole, where aggregates of Ure2p also accumulated. This accumulation of protein aggregates reduced the ability of the Ure2p amyloid seeds to enter budding daughter cells, explaining the cure of daughter cells. This accumulation of protein aggregates mirrors aggresome formation observed in mammalian cells, which may also function to remove potentially harmful protein aggregates. — SMH

EMBO J. 27, 2725 (2008).

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