Calcium depletion challenges endoplasmic reticulum proteostasis by destabilising BiP-substrate complexes
Steffen Preissler1, Claudia Rato1, Yahui Yan1
1Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Elife
|December 9, 2020
Summary
Calcium levels in the endoplasmic reticulum (ER) regulate the Hsp70 chaperone BiP
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- The endoplasmic reticulum (ER) is crucial for protein maturation and calcium storage.
- ER calcium depletion triggers the unfolded protein response (UPR).
- The impact of ER calcium fluctuations on organellar proteostasis remains unclear.
Purpose of the Study:
- To investigate how ER calcium levels affect the Hsp70 chaperone BiP.
- To elucidate the mechanism by which calcium influences BiP-substrate interactions.
- To understand the link between ER calcium, proteostasis, and the UPR.
Main Methods:
- Investigated the effect of calcium on BiP's affinity for ADP.
- Analyzed nucleotide exchange dynamics of BiP in calcium-replete and calcium-depleted ER environments.
- Examined BiP-substrate complex stability under varying calcium conditions.
Main Results:
- Calcium enhances BiP's affinity for ADP in the ER.
- In calcium-replete ER, ADP rebinding favors substrate retention.
- In calcium-depleted ER, accelerated ADP-to-ATP exchange promotes substrate release.
Conclusions:
- Calcium selectively modulates BiP chaperone dynamics by altering its nucleotide-binding properties.
- These findings provide a mechanism for tuning ER quality control in response to calcium signaling.
- This links ER calcium homeostasis to the UPR and cellular stress responses in secretory cells.
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