Please use this identifier to cite or link to this item:
|Title:||Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations||Authors:||Li, Jinyuan Vero
Ju, Lining Arnold
Kuchel, Philip W.
Feneley, Michael P.
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. https://doi.org/10.1038/s42003-021-02528-w||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||URI:||https://scholarbank.nus.edu.sg/handle/10635/232302||ISSN:||2399-3642||DOI:||10.1038/s42003-021-02528-w||Rights:||Attribution 4.0 International|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
|10_1038_s42003-021-02528-w.pdf||3.39 MB||Adobe PDF|
checked on Nov 21, 2022
checked on Nov 17, 2022
This item is licensed under a Creative Commons License