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bioRxiv · 10.1101/617217

Information processing by endoplasmic reticulum stress sensors

Stroberg, W.·Eilertsen, J.·Schnell, S.
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Abstract

The unfolded protein response (UPR) is a collection of cellular feedback mechanisms that seek to maintain protein folding homeostasis in the endoplasmic reticulum (ER). When the ER is \"stressed\", either through high protein folding demand or undersupply of chaperones and foldases, stress sensing proteins in the ER membrane initiate the UPR. Recently, experiments have indicated that these signaling molecules detect stress by being both sequestered by free chaperones and activated by free unfolded proteins. However, it remains unclear what advantage this bidirectional sensor control offers stressed cells. Here, we show that combining positive regulation of sensor activity by unfolded proteins with negative regulation by chaperones allows the sensor to make a more informative measurement of ER stress. The increase in the information capacity of the combined sensing mechanism stems from stretching of the active range of the sensor, at the cost of increased uncertainty due to the integration of multiple signals. These results provide a possible rationale for the evolution of the observed stress sensing mechanism.

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Stroberg, W., Eilertsen, J., Schnell, S.. 2019-04-24. Information processing by endoplasmic reticulum stress sensors. https://doi.org/10.1101/617217

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