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Secretory kinase Fam20C tunes endoplasmic reticulum redox state via phosphorylation of Ero1α
Author(s) -
Zhang Jianchao,
Zhu Qinyu,
Wang Xi'e,
Yu Jiaojiao,
Chen Xinxin,
Wang Jifeng,
Wang Xi,
Xiao Junyu,
Wang Chihchen,
Wang Lei
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798699
Subject(s) - endoplasmic reticulum , biology , phosphorylation , microbiology and biotechnology , kinase , secretory pathway , biochemistry , golgi apparatus
Family with sequence similarity 20C (Fam20C), the physiological Golgi casein kinase, phosphorylates numerous secreted proteins that are involved in a wide variety of biological processes. However, the role of Fam20C in regulating proteins in the endoplasmic reticulum ( ER ) lumen is largely unknown. Here, we report that Fam20C interacts with various luminal proteins and that its depletion results in a more reduced ER lumen. We further show that ER oxidoreductin 1α (Ero1α), the pivotal sulfhydryl oxidase that catalyzes disulfide formation in the ER , is phosphorylated by Fam20C in the Golgi apparatus and retrograde‐transported to the ER mediated by ER p44. The phosphorylation of Ser145 greatly enhances Ero1α oxidase activity and is critical for maintaining ER redox homeostasis and promoting oxidative protein folding. Notably, phosphorylation of Ero1α is induced under hypoxia, reductive stress, and secretion‐demanding conditions such as mammalian lactation. Collectively, our findings open a door to uncover how oxidative protein folding is regulated by phosphorylation in the secretory pathway.