Related Experiment Video
Updated: Sep 18, 2025
11:40
Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics
Published on: June 23, 2022
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Extracellular Matrix Proximity Biotinylation Identifies Periostin as a PHEX Proteolytic Substrate
Chirada Dusadeemeelap1, Takuma Matsubara2, Shoichiro Kokabu2
1Department of General Dentistry, Faculty of Dentistry, Srinakharinwirot University, Bangkok, Thailand.
Summary
Inactivating PHEX gene mutations cause X-linked hypophosphatemia (XLH), affecting bone mineralization. This study identifies PHEX interactors, revealing its role in bone matrix regulation and potential XLH mechanisms.
Area of Science:
- Biochemistry
- Genetics
- Cell Biology
Background:
- X-linked hypophosphatemia (XLH) stems from inactivating PHEX gene mutations.
- XLH impairs skeletal mineralization, causing rickets and osteomalacia due to osteoblast dysfunction.
- PHEX, an endopeptidase in osteoblasts, has poorly understood substrates and interactions.
Purpose of the Study:
- To identify the extracellular proximal interactome of PHEX in osteoblasts.
- To understand PHEX function in bone matrix regulation.
- To uncover mechanisms underlying XLH pathogenesis.
Main Methods:
- Proximity-dependent biotin identification (BioID2) coupled with affinity purification and mass spectrometry.
- Tagging the PHEX extracellular domain with BioID2 in osteoblasts.
- Validation of protein interactions and enzymatic activity.
Main Results:
- A PHEX proximity network of 39 high-confidence proteins was identified.
- Key proteins involved in bone morphogenesis and matrix organization were found.
- Proteolytic cleavage of periostin by PHEX was confirmed.
Conclusions:
- BioID2 is effective for studying osteoblast cell-matrix interactions.
- A novel PHEX interactome map provides insights into PHEX function.
- This research offers a valuable resource for understanding XLH mechanisms.
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