Research Data Leeds Repository

Sphingomyelinase Disables Inactivation in Endogenous PIEZO1 Channels

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 C 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:	Location Type http://eprints.whiterose.ac.uk/165506/ Publication https://doi.org/10.1016/j.celrep.2020.108225 Publication
License:	Creative Commons Attribution 4.0 International (CC BY 4.0)
Date deposited:	10 Nov 2020 14:24
URI:	http://archive.researchdata.leeds.ac.uk/id/eprint/770
Additional details Additional details Creators: Creators ORCID Other ID Email Primary affiliation Primary affiliation ID Primary affiliation ID type Secondary affiliation Secondary affiliation ID Secondary affiliation ID type Shi, Jian https://orcid.org/0000-0003-2179-8579 University Of Leeds https://doi.org/10.13039/501100000777 crossref Hyman, Adam J https://orcid.org/0000-0003-0874-6678 De Vecchis, Dario https://orcid.org/0000-0002-7732-5095 Chong, Jiehan https://orcid.org/0000-0002-5846-7397 University Of Leeds https://doi.org/10.13039/501100000777 crossref Lichtenstein, Laeticia https://orcid.org/0000-0003-3900-786X University Of Leeds https://doi.org/10.13039/501100000777 crossref Futers, Simon T https://orcid.org/0000-0003-3810-190X University Of Leeds https://doi.org/10.13039/501100000777 crossref Rouahi, Myriam Negre Salvayre, Anne https://orcid.org/0000-0003-2136-5706 Auge, Nathalie https://orcid.org/0000-0003-2088-7211 Kalli, Antreas C https://orcid.org/0000-0001-7156-9403 University Of Leeds https://doi.org/10.13039/501100000777 crossref Beech, David J https://orcid.org/0000-0002-7683-9422 University Of Leeds https://doi.org/10.13039/501100000777 crossref Type of data: Dataset Research funders: British Heart Foundation, British Heart Foundation, Wellcome Trust, Academy of Medical Sciences and Welllcome Trust, INSERM, BBSRC, MRC Grant numbers: FS/17/2/32559, RG/17/11/33042, 110044/Z/15/Z, SBF002 \1031, 1360947, MR/R01745X/1 Publication date: 2020 Resource language: English Metadata language: English Publisher: University of Leeds Contact Email Address: A.Kalli@leeds.ac.uk Last Modified: 11 Nov 2020 14:57

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Documentation

Zip file contents [9kB] Zip file contents [9kB] Zip file contents [9kB] Visible to: Anyone File name: contents_zip_DOI725.xlsx Content type: Documentation Mime-Type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 9kB

Data

Simulation data for Piezo1 [7GB] Simulation data for Piezo1 [7GB] Simulation data for Piezo1 [7GB] Visible to: Anyone File name: simulation_data_for_Piezo1.zip Content type: Data Mime-Type: application/zip License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 7GB