Membrane curvature governs the distribution of Piezo1 in live cells

Shilong Yang, Xinwen Miao, Steven Arnold, Boxuan Li, Alan T. Ly, Huan Wang, Matthew Wang, Xiangfu Guo, Medha M. Pathak, Wenting Zhao, Charles D. Cox and Zheng Shi ()
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Shilong Yang: Rutgers University
Xinwen Miao: Nanyang Technological University
Steven Arnold: Rutgers University
Boxuan Li: Rutgers University
Alan T. Ly: UC Irvine
Huan Wang: Rutgers University
Matthew Wang: Rutgers University
Xiangfu Guo: Nanyang Technological University
Medha M. Pathak: UC Irvine
Wenting Zhao: Nanyang Technological University
Charles D. Cox: Victor Chang Cardiac Research Institute
Zheng Shi: Rutgers University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35034-6

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