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Analysis of Minerals Produced by hFOB 1.19 and Saos-2 Cells Using Transmission Electron Microscopy with Energy Dispersive X-ray Microanalysis
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Inorganic polyphosphate controls cyclophilin B-mediated collagen folding in osteoblast-like cells
Mei Li Khong1, Lina Li1, Maria E Solesio2
1School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, China.
The FEBS Journal
|February 15, 2020
Summary
Inorganic polyphosphate (polyP) regulates collagen folding in the endoplasmic reticulum by inhibiting cyclophilin B. This finding reveals polyP as a key controller of protein homeostasis in the ER.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Inorganic polyphosphate (polyP) plays diverse biological roles.
- PolyP is abundant in osteoblasts, but its specific functions remain unclear.
- The endoplasmic reticulum (ER) is crucial for protein folding and homeostasis.
Purpose of the Study:
- To investigate the function of inorganic polyphosphate (polyP) in higher eukaryotes.
- To determine the role of polyP in protein folding within the endoplasmic reticulum (ER).
- To elucidate the interaction between polyP and cyclophilin B (CypB) in collagen folding.
Main Methods:
- Utilized osteoblastic SaOS-2 cell line as a model system.
- Investigated the localization of polyP within the ER.
- Performed biochemical assays to confirm direct binding of polyP to CypB.
- Assessed the effect of polyP on CypB's peptidyl-prolyl cis-trans isomerase activity.
- Manipulated cellular polyP levels using spermine sequestration and polyphosphatase expression.
Main Results:
- PolyP was found to be highly enriched in the ER and colocalized with cyclophilin B (CypB).
- PolyP directly binds to CypB, inhibiting its enzymatic activity essential for collagen folding.
- Reducing cellular polyP levels (via spermine or polyphosphatase) decreased collagen misfolding.
- Endogenous polyP was confirmed to regulate CypB-mediated collagen folding.
Conclusions:
- Inorganic polyphosphate (polyP) is a critical regulator of protein homeostasis within the ER.
- PolyP directly modulates cyclophilin B activity, thereby controlling collagen folding.
- This study identifies a novel role for polyP as a molecular chaperone or regulator in the ER environment.
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