@article{c665d03fc4d64de8b8a30b77555c1a8b,
title = "Membrane curvature governs the distribution of Piezo1 in live cells",
abstract = "Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of Piezo1 within a cell is essential for various biological processes including cytokinesis, cell migration, and wound healing. However, the underlying principles that guide the subcellular distribution of Piezo1 remain largely unexplored. Here, we demonstrate that membrane curvature serves as a key regulator of the spatial distribution of Piezo1 in the plasma membrane of living cells. Piezo1 depletes from highly curved membrane protrusions such as filopodia and enriches to nanoscale membrane invaginations. Quantification of the curvature-dependent sorting of Piezo1 directly reveals the in situ nano-geometry of the Piezo1-membrane complex. Piezo1 density on filopodia increases upon activation, independent of calcium, suggesting flattening of the channel upon opening. Consequently, the expression of Piezo1 inhibits filopodia formation, an effect that diminishes with channel activation.",
author = "Shilong Yang and Xinwen Miao and Steven Arnold and Boxuan Li and Ly, {Alan T.} and Huan Wang and Matthew Wang and Xiangfu Guo and Pathak, {Medha M.} and Wenting Zhao and Cox, {Charles D.} and Zheng Shi",
note = "Funding Information: The authors are grateful for a critical review of a preprint version of this manuscript (https://sciety.org/articles/activity/10.1101/2022.06.22.497259) by Alec Nickolls, Ruhma Syeda, Bailong Xiao, and Alex Chesler. We thank Bailong Xiao lab for providing quantifications of CryoEM images of Piezo1 containing liposomes. We thank Gill Fitz and Matt Tyska for helpful suggestions on filopodia quantification. We thank Bineet Sharma and Joyce Lin for a careful proofread of the manuscript. We thank Ben Schuster lab for access to confocal microscopy, Renping Zhou, Zhiping Pang, and Tibor Rohacs labs for helping with cell culture. We thank Markus Deserno, Padmini Rangamani, Bianxiao Cui, Elizabeth Kelley, Navid Bavi, Rod MacKinnon, Liqun Luo, Jiefu Li, Jie Xu, Andy Nieuwkoop, Deirdre O{\textquoteright}Carroll, and Rick Remsing for helpful discussions. The project is supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Award Number R35GM147027 (Z.S.) and by the National Institute on Drug Abuse, the National Institute of Neurological Disorders and Stroke, and the National Institute of Mental Health of the NIH under Award Number R21DA056322 (Z.S.). H.W. is supported by the Zhou family fellowship. A.T.L. acknowledges the R01(NS10981) Diversity Supplement and NIH F31 1F31NS127594-0. M.M.P acknowledges R01NS109810. W.Z. acknowledges the funding supports from the Singapore Ministry of Education (MOE) RG95/21 and the Human Frontier Science Program Foundation RGY0088/2021. Funding Information: The authors are grateful for a critical review of a preprint version of this manuscript ( https://sciety.org/articles/activity/10.1101/2022.06.22.497259 ) by Alec Nickolls, Ruhma Syeda, Bailong Xiao, and Alex Chesler. We thank Bailong Xiao lab for providing quantifications of CryoEM images of Piezo1 containing liposomes. We thank Gill Fitz and Matt Tyska for helpful suggestions on filopodia quantification. We thank Bineet Sharma and Joyce Lin for a careful proofread of the manuscript. We thank Ben Schuster lab for access to confocal microscopy, Renping Zhou, Zhiping Pang, and Tibor Rohacs labs for helping with cell culture. We thank Markus Deserno, Padmini Rangamani, Bianxiao Cui, Elizabeth Kelley, Navid Bavi, Rod MacKinnon, Liqun Luo, Jiefu Li, Jie Xu, Andy Nieuwkoop, Deirdre O{\textquoteright}Carroll, and Rick Remsing for helpful discussions. The project is supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Award Number R35GM147027 (Z.S.) and by the National Institute on Drug Abuse, the National Institute of Neurological Disorders and Stroke, and the National Institute of Mental Health of the NIH under Award Number R21DA056322 (Z.S.). H.W. is supported by the Zhou family fellowship. A.T.L. acknowledges the R01(NS10981) Diversity Supplement and NIH F31 1F31NS127594-0. M.M.P acknowledges R01NS109810. W.Z. acknowledges the funding supports from the Singapore Ministry of Education (MOE) RG95/21 and the Human Frontier Science Program Foundation RGY0088/2021. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-35034-6",
language = "English (US)",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}