Piezo2 is a mechanosensitive ion channel that plays critical roles in sensing touch and pain, proprioception, and regulation of heart rate. Global knockout of Piezo2 leads to perinatal lethality in mice, and Piezo2 gain-of-function mutations are associated with distal arthrogryposis, a disease characterized by congenital joint contractures. Emerging evidence suggests that Piezo channels (Piezo1 and Piezo2) can be regulated by their local membrane environment and particularly by cholesterol and phosphoinositides. To characterize the local Piezo2 lipid environment and investigate key lipid–protein interactions, we carried out coarse-grained molecular dynamics simulations of Piezo2 embedded in a complex mammalian membrane containing >60 distinct lipid species. We show that Piezo2 alters its local membrane composition such that it becomes enriched with specific lipids, such as phosphoinositides, and forms specific, long-term interactions with a variety of lipids at functionally relevant sites.
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Communication|
Mechanotransduction by Membrane Proteins|
July 21 2022
Characterizing the lipid fingerprint of the mechanosensitive channel Piezo2
Yiechang Lin
,
Yiechang Lin
1
Research School of Biology, Canberra, Australia
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Amanda Buyan
,
Amanda Buyan
1
Research School of Biology, Canberra, Australia
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Ben Corry
1
Research School of Biology, Canberra, Australia
Correspondence to Ben Corry: ben.corry@anu.edu.au
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Yiechang Lin
1
Research School of Biology, Canberra, Australia
Amanda Buyan
1
Research School of Biology, Canberra, Australia
Correspondence to Ben Corry: ben.corry@anu.edu.au
Received:
November 23 2021
Revision Received:
May 22 2022
Accepted:
July 01 2022
Online Issn: 1540-7748
Print Issn: 0022-1295
Funding
Funder(s):
Australian Research Council
- Award Id(s): DP200100860
Funder(s):
National Computational Infrastructure
Funder(s):
Australasian Leadership Computing Grants scheme
© 2022 Lin et al.
2022
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Gen Physiol (2022) 154 (10): e202113064.
Article history
Received:
November 23 2021
Revision Received:
May 22 2022
Accepted:
July 01 2022
Citation
Yiechang Lin, Amanda Buyan, Ben Corry; Characterizing the lipid fingerprint of the mechanosensitive channel Piezo2. J Gen Physiol 3 October 2022; 154 (10): e202113064. doi: https://doi.org/10.1085/jgp.202113064
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