Piezo1 ion channels are capable of conformational signaling.

dc.contributor.author

Lewis, Amanda H

dc.contributor.author

Cronin, Marie E

dc.contributor.author

Grandl, Jörg

dc.date.accessioned

2024-07-01T14:00:41Z

dc.date.available

2024-07-01T14:00:41Z

dc.date.issued

2024-05-29

dc.description.abstract

Piezo1 is a mechanically activated ion channel that senses forces with short latency and high sensitivity. Piezos undergo large conformational changes, induce far-reaching deformation onto the membrane, and modulate the function of two-pore potassium (K2P) channels. Taken together, this led us to hypothesize that Piezos may be able to signal their conformational state to other nearby proteins. Here, we use chemical control to acutely restrict Piezo1 conformational flexibility and show that Piezo1 conformational changes, but not ion permeation through it, are required for modulating the K2P channel TREK1. Super-resolution imaging and stochastic simulations further reveal that both channels do not co-localize, which implies that modulation is not mediated through direct binding interactions; however, at high Piezo1 densities, most TREK1 channels are within the predicted Piezo1 membrane footprint, suggesting the footprint may underlie conformational signaling. We speculate that physiological roles originally attributed to Piezo1 ionotropic function could, alternatively, involve conformational signaling.

dc.identifier

2024.05.28.596257

dc.identifier.uri

https://hdl.handle.net/10161/31225

dc.language

eng

dc.relation.ispartof

bioRxiv

dc.relation.isversionof

10.1101/2024.05.28.596257

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.title

Piezo1 ion channels are capable of conformational signaling.

dc.type

Journal article

duke.contributor.orcid

Grandl, Jörg|0000-0001-7179-7609

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Cell Biology

pubs.organisational-group

Neurobiology

pubs.organisational-group

University Institutes and Centers

pubs.organisational-group

Duke Institute for Brain Sciences

pubs.publication-status

Published online

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