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Title: Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations
Authors: Li, Jinyuan Vero
Ng, Chai-Ann
Cheng, Delfine
Zhou, Zijing
Yao, Mingxi 
Guo, Yang
Yu, Ze-Yan
Ramaswamy, Yogambha
Ju, Lining Arnold
Kuchel, Philip W.
Feneley, Michael P.
Fatkin, Diane
Cox, Charles D.
Issue Date: 6-Sep-2021
Publisher: Nature Research
Citation: Li, Jinyuan Vero, Ng, Chai-Ann, Cheng, Delfine, Zhou, Zijing, Yao, Mingxi, Guo, Yang, Yu, Ze-Yan, Ramaswamy, Yogambha, Ju, Lining Arnold, Kuchel, Philip W., Feneley, Michael P., Fatkin, Diane, Cox, Charles D. (2021-09-06). Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations. Communications Biology 4 (1) : 1038. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Mechanosensitive channels are integral membrane proteins that sense mechanical stimuli. Like most plasma membrane ion channel proteins they must pass through biosynthetic quality control in the endoplasmic reticulum that results in them reaching their destination at the plasma membrane. Here we show that N-linked glycosylation of two highly conserved asparagine residues in the ‘cap’ region of mechanosensitive Piezo1 channels are necessary for the mature protein to reach the plasma membrane. Both mutation of these asparagines (N2294Q/N2331Q) and treatment with an enzyme that hydrolyses N-linked oligosaccharides (PNGaseF) eliminates the fully glycosylated mature Piezo1 protein. The N-glycans in the cap are a pre-requisite for N-glycosylation in the ‘propeller’ regions, which are present in loops that are essential for mechanotransduction. Importantly, trafficking-defective Piezo1 variants linked to generalized lymphatic dysplasia and bicuspid aortic valve display reduced fully N-glycosylated Piezo1 protein. Thus the N-linked glycosylation status in vitro correlates with efficient membrane trafficking and will aid in determining the functional impact of Piezo1 variants of unknown significance. © 2021, The Author(s).
Source Title: Communications Biology
ISSN: 2399-3642
DOI: 10.1038/s42003-021-02528-w
Rights: Attribution 4.0 International
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