Cell Biology

Sorting Out the Trash

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Science  05 Jan 2007:
Vol. 315, Issue 5808, pp. 19
DOI: 10.1126/science.315.5808.19a

When cells accumulate large quantities of proteins that have been damaged (for instance, via modification by reactive oxygen species) or that have not folded properly (for instance, as a result of mutations associated with neurodegenerative diseases), the degradative capacity of the intra-cellular quality-control system can be overwhelmed. Under these conditions, the aberrant proteins collect to form an aggresome, which is an inclusion body situated close to the micro-tubule-organizing center and just outside of the nucleus.

Rujano et al. examined the fate of cultured cells containing an aggresome, and of the aggresomes themselves, as the cells divided. Do aggresome-containing cells complete mitosis successfully? Are both daughter cells equally likely to inherit the parental garbage, or is one daughter preferentially spared? They found that aggresome-containing cells could indeed progress through mitosis productively and that the pre-existing aggresome was inherited asymmetrically, yielding daughter cells relatively poor (or rich) in damaged proteins. Furthermore, a survey of cells in the epithelial crypts of the small intestine in two spinocerebellar ataxia (a neurodegenerative disorder) patients revealed a systematic allocation of the protein inclusions to the short-lived differentiated daughter cells, presumably ensuring the preservation of long-lived stem cells. — SMH

PLoS Biol. 4, e417 (2006).

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