@article{733a7c83824a44d380c36e6b905c28ac,
title = "Inorganic polyphosphate controls cyclophilin B-mediated collagen folding in osteoblast-like cells",
abstract = "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.",
keywords = "SaOS-2 cells, collagen folding, cyclophilin B, osteoblast-like cells, polyphosphate",
author = "Khong, {Mei Li} and Lina Li and Solesio, {Maria E.} and Pavlov, {Evgeny V.} and Tanner, {Julian A.}",
note = "Funding Information: This research was supported by Hong Kong UGC GRF Grant HKU 776507M to JAT. and National Institute of Health grant (GM115570‐01A1) to EVP. We thank Dr. Kathryn Cheah of the University of Hong Kong (HKU) for constructive comments on the manuscript; Dr. Kalle Gehring from McGill University for providing the pGEX‐6P‐1‐CypB plasmid crucial for our biochemical work; Dr. Kathryn Cheah{\textquoteright}s laboratories (HKU) for the anti‐calnexin and anti‐Col I primary antibodies; and Dr. Young‐Tae Chang from National University of Singapore for the JC‐D8 probes used in our microscopy experiments. We thank Mr. Charlie Lang Yen‐Po (HKU) for the design of the inverted native–PAGE. We are grateful to the Faculty Core Facility in HKU, Dr. Yee‐Wai Cheung (HKU), Dr. Andrew Brian Kinghorn (HKU), and Dr. Federico Giuseppe Amodeo from New York University for all the technical advice given. Funding Information: This research was supported by Hong Kong UGC GRF Grant HKU 776507M to JAT. and National Institute of Health grant (GM115570-01A1) to EVP. We thank Dr. Kathryn Cheah of the University of Hong Kong (HKU) for constructive comments on the manuscript; Dr. Kalle Gehring from McGill University for providing the pGEX-6P-1-CypB plasmid crucial for our biochemical work; Dr. Kathryn Cheah{\textquoteright}s laboratories (HKU) for the anti-calnexin and anti-Col I primary antibodies; and Dr. Young-Tae Chang from National University of Singapore for the JC-D8 probes used in our microscopy experiments. We thank Mr. Charlie Lang Yen-Po (HKU) for the design of the inverted native–PAGE. We are grateful to the Faculty Core Facility in HKU, Dr. Yee-Wai Cheung (HKU), Dr. Andrew Brian Kinghorn (HKU), and Dr. Federico Giuseppe Amodeo from New York University for all the technical advice given. Publisher Copyright: {\textcopyright} 2020 Federation of European Biochemical Societies",
year = "2020",
month = oct,
day = "1",
doi = "10.1111/febs.15249",
language = "English (US)",
volume = "287",
pages = "4500--4524",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "20",
}