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Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons

Author

Listed:
  • Yanmei Qi

    (Sensory Mechanotransduction, Centre for Integrative Neuroscience)

  • Laura Andolfi

    (Istituto Officina dei Materiali Consiglio Nazionale delle Ricerche)

  • Flavia Frattini

    (Sensory Mechanotransduction, Centre for Integrative Neuroscience)

  • Florian Mayer

    (Sensory Mechanotransduction, Centre for Integrative Neuroscience)

  • Marco Lazzarino

    (Istituto Officina dei Materiali Consiglio Nazionale delle Ricerche)

  • Jing Hu

    (Sensory Mechanotransduction, Centre for Integrative Neuroscience)

Abstract

Sensing force is crucial to maintain the viability of all living cells. Despite its fundamental importance, how force is sensed at the molecular level remains largely unknown. Here we show that stomatin-like protein-3 (STOML3) controls membrane mechanics by binding cholesterol and thus facilitates force transfer and tunes the sensitivity of mechano-gated channels, including Piezo channels. STOML3 is detected in cholesterol-rich lipid rafts. In mouse sensory neurons, depletion of cholesterol and deficiency of STOML3 similarly and interdependently attenuate mechanosensitivity while modulating membrane mechanics. In heterologous systems, intact STOML3 is required to maintain membrane mechanics to sensitize Piezo1 and Piezo2 channels. In C57BL/6N, but not STOML3−/− mice, tactile allodynia is attenuated by cholesterol depletion, suggesting that membrane stiffening by STOML3 is essential for mechanical sensitivity. Targeting the STOML3–cholesterol association might offer an alternative strategy for control of chronic pain.

Suggested Citation

  • Yanmei Qi & Laura Andolfi & Flavia Frattini & Florian Mayer & Marco Lazzarino & Jing Hu, 2015. "Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9512
    DOI: 10.1038/ncomms9512
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    Cited by:

    1. 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.
    2. Max Lundberg & Alexander Mackintosh & Anna Petri & Staffan Bensch, 2023. "Inversions maintain differences between migratory phenotypes of a songbird," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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