CELL BIOLOGY: Astrocytes and Stress

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Science  11 Feb 2005:
Vol. 307, Issue 5711, pp. 817b
DOI: 10.1126/science.307.5711.817b

Eukaryotic cells sense stressful conditions, such as the accumulation of abnormal proteins, in their endoplasmic reticulum (ER) by means of the aptly named unfolded protein response (UPR). As a protective mechanism, the UPR system activates the expression of damage-control proteins, such as the ER protein-folding chaperonin BiP. Kondo et al. have determined that astrocytes of the central nervous system employ an ER stress transducer called old astrocyte specifically induced substance (OASIS). OASIS is an ER transmembrane protein in the same transcription factor family as CREB/ATF. When astrocytes were treated with agents that disrupt protein glycosylation or calcium homeostasis in the ER, OASIS was cleaved, and its N-terminal domain moved into the nucleus. This fragment stimulated transcription by activating a promoter with known ER stress-responsive elements (ERSEs). ER stress induced OASIS expression in astrocytes but not in neurons or fibroblasts. Knockdown of OASIS expression reduced the expression of BiP, whereas OASIS overexpression conferred resistance to cell death in response to ER stress. Thus, astrocytes may utilize a cell type-specific mechanism to survive stress induced by ischemic or hypoxic conditions. — LDC

Nature Cell Biol. 10.1038/ncb1213 (2005).

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