Ca²⁺-driven PDIA6 biomolecular condensation ensures proinsulin folding.

ABSTRACT: The endoplasmic reticulum (ER) plays crucial roles in maintaining protein quality control and regulating dynamic Ca²⁺ storage in eukaryotic cells. However, the proteostasis system involved in ER-mediated protein quality control has not been fully characterized. Here we show that Ca²⁺ triggers the condensation of PDIA6, an ER-resident disulfide isomerase and molecular chaperone, into quality control granules. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the PDIA6 condensates recruit proinsulin, thereby accelerating the oxidative proinsulin fo

SUBMITTER: Lee YH 

PROVIDER: S-EPMC12611771 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature