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PreprintCited by 6Ion channel regulation and functionIon Channels and ReceptorsErythrocyte Function and Pathophysiology

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Tentonin 3 is a pore-forming subunit of a slow-inactivation mechanosensitive channel

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Pak, Sungmin, Ryu, Hyunil, Nguyen, Thien-Luan, Lim, Sujin, Kang, Su Min, Yu, Yeon Gyu, Woo, Junhyuk, Kim, Chanjin, Fenollar-Ferrer, Cristina, Wood, John N, Lee, Mi-Ock, Hong, Gyu-Sang, Han, Kyungreem, Kim, Tae Song, Oh, Uhtaek·2023·Cell Reports
DOI 10.21203/rs.3.rs-2785213/v1PMC PMC11310380

Preprint — published as 10.1016/j.celrep.2024.114334 · Paper page

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Abstract

Mechanically activating (MA) channels transduce numerous physiological functions. Tentonin 3/TMEM150C (TTN3) confers MA currents with slow-inactivation kinetics in somato- and baro-sensory neurons. Despite the distinct currents when heterologously expressed, whether TTN3 forms a channel pore is unknown. Here, we demonstrate that purified TTN3 proteins incorporated into the lipid bilayer exhibited spontaneous and pressure-sensitive channel currents. MA currents of TTN3 with unique slow-inactivation kinetics were conserved throughout the vertebrate phyla. The activation threshold of TTN3 and its pharmacological perturbations separated TTN3 from Piezo1. Deep neural network structure prediction programmes coupled with mutagenetic analysis predicted a rectangular shaped, tetrameric structure with six transmembrane helices and a pore at the inter-subunit centre. The putative pore aligned with two helices of each subunit and had constriction sites whose mutations changed the MA currents. These results suggest that TTN3 is a pore-forming subunit of a slow-inactivation MA channel, possibly with a unique structure.

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Metadata

Authors
Pak, S., Ryu, H., Nguyen, T.-L., Lim, S., Kang, S. M., Yu, Y. G., Woo, J., Kim, C., Fenollar-Ferrer, C., Wood, J. N., Lee, M.-O., Hong, G.-S., Han, K., Kim, T. S., & Oh, U.
Affiliations
  • Seoul National University (KR)
  • Korea Institute of Science and Technology (KR)
  • Seoul National University
  • Kookmin University
  • Kookmin University (KR)
  • Florida Atlantic University
  • University College London (GB)
  • Seoul National University of Science and Technology (KR)
Corresponding author
  • Hong, Gyu-Sang
  • Han, Kyungreem
  • Kim, Tae Song
  • Oh, Uhtaek
ORCID
Venue
Cell Reports
Publisher
Springer Science and Business Media LLC
Published
2023-04-07
Volume
43
Issue
6
Pages
114334-114334
ISSN
2211-1247 (ISSN-L)
DOI
10.21203/rs.3.rs-2785213/v1
PMC
PMC11310380
OpenAlex
W4399418647
Cited by
6
References
2
Citations by year
2026: 2 · 2025: 2 · 2024: 2
FWCI
0.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Palm Healthcare Foundation
  • National Research Foundation
  • Korea Institute of Science and Technology (2Z06588, 2E32231)
  • National Research Foundation of Korea (NRF-2020R1C1C101024513, NRF-2022M3E5E801739512, RS-2023-00254795, 2020R1A2C210036313, 2020R1A2C1101174, NRF- 2020R1A3A300192913)
  • National Institutes of Health
  • National Institute on Deafness and Other Communication Disorders (DC000039, T32DC000039, Z01DC000039)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Physiology (medical) › Erythrocyte Function and Pathophysiology
Keywords
mechanosensitive ion channels, slow inactivation, pore-forming subunit, Piezo1, somatosensory neurons, transmembrane helices, mutagenesis
MeSH terms
Amino Acid Sequence, Animals, Humans, Ion Channels, Lipid Bilayers, Membrane Proteins, Mutation, Protein Subunits, Mechanotransduction, Cellular, Mice, HEK293 Cells

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