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Sphingomyelinase Disables Inactivation in Endogenous PIEZO1 Channels

Citation

Shi, Jian and Hyman, Adam J. and De Vecchis, Dario and Chong, Jiehan and Lichtenstein, Laeticia and Futers, Simon T. and Rouahi, Myriam and Negre Salvayre, Anne and Auge, Nathalie and Kalli, Antreas and Beech, David J. (2020) Sphingomyelinase Disables Inactivation in Endogenous PIEZO1 Channels. University of Leeds. [Dataset] https://doi.org/10.5518/725

Dataset description

Endogenous PIEZO1 channels of native endothelium lack the hallmark inactivation often seen when these channels are overexpressed in cell lines. Because prior work showed that the force of shear stress activates sphingomyelinase in endothelium, we considered if sphingomyelinase is relevant to endogenous PIEZO1. Patch clamping was used to quantify PIEZO1-mediated signals in freshly isolated murine endothelium exposed to the mechanical forces caused by shear stress and membrane stretch. Neutral sphingomyelinase inhibitors and genetic disruption of sphingomyelin phosphodiesterase 3 (SMPD3) cause PIEZO1 to switch to profoundly inactivating behavior. Ceramide (a key product of SMPD3) rescues non-inactivating channel behavior. Its co-product, phosphoryl choline, has no effect. In contrast to ceramide, sphingomyelin (the SMPD3 substrate) does not affect inactivation but alters channel force sensitivity. The data suggest that sphingomyelinase activity, ceramide, and sphingomyelin are determinants of native PIEZO gating that enable sustained activity.

Keywords: PIEZO1, inactivation, endothelium, sphingomyelinase, SMPD3, ceramide, sphingomyelin, mechanically activated channel, molecular dynamics, simualtions
Subjects: A000 - Medicine & dentistry
Divisions: Faculty of Medicine and Health > School of Medicine
Related resources:
LocationType
https://eprints.whiterose.ac.uk/165506/Publication
https://doi.org/10.1016/j.celrep.2020.108225Publication
License: Creative Commons Attribution 4.0 International (CC BY 4.0)
Date deposited: 10 Nov 2020 14:24
URI: https://archive.researchdata.leeds.ac.uk/id/eprint/770

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