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Inorganic polyphosphate controls cyclophilin B‐mediated collagen folding in osteoblast‐like cells
Author(s) -
Khong Mei Li,
Li Lina,
Solesio Maria E.,
Pavlov Evgeny V.,
Tanner Julian A.
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15249
Subject(s) - endoplasmic reticulum , prolyl isomerase , unfolded protein response , microbiology and biotechnology , peptidylprolyl isomerase , chemistry , protein folding , polyphosphate , cyclophilin , osteoblast , biochemistry , folding (dsp implementation) , regulator , isomerase , protein disulfide isomerase , pin1 , biology , enzyme , in vitro , gene , phosphate , electrical engineering , engineering
Evidence is emerging that inorganic polyphosphate (polyP) is a fundamental molecule involved in a wide range of biological processes. In higher eukaryotes, polyP is abundant in osteoblasts but questions remain as to its functions. Here, we find that polyP is particularly enriched in endoplasmic reticulum (ER) where it colocalizes with cyclophilin B (CypB) using osteoblastic SaOS‐2 model cell line. PolyP binds directly and specifically to CypB, inhibiting its peptidyl‐prolyl cis‐trans isomerase activity which is critical for collagen folding. PolyP sequestration by spermine and ER‐specific polyP reduction by polyphosphatase expression in cells reduced collagen misfolding and confirmed that endogenous polyP acts as a molecular control of CypB‐mediated collagen folding. We propose that polyP is a previously unrecognized critical regulator of protein homeostasis in ER.