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Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch

Author

Listed:
  • Kate Poole

    (Max-Delbrück Center for Molecular Medicine)

  • Regina Herget

    (Max-Delbrück Center for Molecular Medicine)

  • Liudmila Lapatsina

    (Max-Delbrück Center for Molecular Medicine)

  • Ha-Duong Ngo

    (Microsensor & Actuator Technology, Technische Universität Berlin)

  • Gary R. Lewin

    (Max-Delbrück Center for Molecular Medicine)

Abstract

In sensory neurons, mechanotransduction is sensitive, fast and requires mechanosensitive ion channels. Here we develop a new method to directly monitor mechanotransduction at defined regions of the cell-substrate interface. We show that molecular-scale (~13 nm) displacements are sufficient to gate mechanosensitive currents in mouse touch receptors. Using neurons from knockout mice, we show that displacement thresholds increase by one order of magnitude in the absence of stomatin-like protein 3 (STOML3). Piezo1 is the founding member of a class of mammalian stretch-activated ion channels, and we show that STOML3, but not other stomatin-domain proteins, brings the activation threshold for Piezo1 and Piezo2 currents down to ~10 nm. Structure–function experiments localize the Piezo modulatory activity of STOML3 to the stomatin domain, and higher-order scaffolds are a prerequisite for function. STOML3 is the first potent modulator of Piezo channels that tunes the sensitivity of mechanically gated channels to detect molecular-scale stimuli relevant for fine touch.

Suggested Citation

  • Kate Poole & Regina Herget & Liudmila Lapatsina & Ha-Duong Ngo & Gary R. Lewin, 2014. "Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4520
    DOI: 10.1038/ncomms4520
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    Cited by:

    1. Timo A. Nees & Na Wang & Pavel Adamek & Nadja Zeitzschel & Clement Verkest & Carmen Porta & Irina Schaefer & Julie Virnich & Selin Balkaya & Vincenzo Prato & Chiara Morelli & Valerie Begay & Young Jae, 2023. "Role of TMEM100 in mechanically insensitive nociceptor un-silencing," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Julia Ojeda-Alonso & Laura Calvo-Enrique & Ricardo Paricio-Montesinos & Rakesh Kumar & Ming-Dong Zhang & James F. A. Poulet & Patrik Ernfors & Gary R. Lewin, 2024. "Sensory Schwann cells set perceptual thresholds for touch and selectively regulate mechanical nociception," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Martina Nicoletti & Letizia Chiodo & Alessandro Loppini, 2021. "Biophysics and Modeling of Mechanotransduction in Neurons: A Review," Mathematics, MDPI, vol. 9(4), pages 1-32, February.

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