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The Molecular Mechanism of Multifunctional Mechano-Gated Channel TRPV4

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Book cover Mechanically Gated Channels and their Regulation

Part of the book series: Mechanosensitivity in Cells and Tissues ((MECT,volume 6))

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Abstract

Transient receptor potential vanilloid 4 (TRPV4) is a member of the TRP family of channels. It contains 6 transmembrane domains and was first identified as a hypoosmolality-activated Ca2+ permeable channel. TRPV4 is functionally active in many tissues, including nerve, bone, lung, kidney and blood vessels. Hypoosmolality activates phospholipase A2 (PLA2), which produces eicosanoids indirectly that open TRPV4. TRPV4 is also a direct mechano-sensitive channel, and cytoskeleton proteins such as actin, tubulin and integrin bind to the channel, helping it to respond to mechanical stimuli. The channel is able to sense diverse physical stimuli, such as warmth, inflammation and fluid flow, and thus can be considered a multifunctional micro-machine. After TRPV4 activation, released for example ATP transmits a signal to nerve endings via purinergic receptors or initiates dynamic changes in the cytoskeleton to modify cell structure. TRPV4-null mice exhibit an almost normal appearance, but lack mechano-sensation in various tissues under variable stresses. Gain-of-function mutations in the channel, in humans, lead to skeletal limb deformities and neuromuscular dysplasia with sensory abnormalities. Loss of function mutations lead to late onset hyponatremia or peripheral arthropathy. A thorough understanding of the molecular mechanisms of TRPV4 function will provide insight into how disruptions in mechanical signal transduction cause disease.

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Acknowledgements

This work was supported by grants-in-aid for scientific research (22590291). We would like to thank Shigematsu for helpful comment and photo.

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Authors and Affiliations

  1. Edogawabashi clinic, 348 Yamabuki, Shinjyuku, Tokyo, Japan

    Makoto Suzuki

  2. Department of Molecular Pharmacology, Jichi Medical university, Yakushiji 3311-1, Tochigi, Japan

    Astuko Mizuno

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  1. Makoto Suzuki
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  2. Astuko Mizuno
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Correspondence to Makoto Suzuki .

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Editors and Affiliations

  1. Chemical Department, Moscow State University, Vorobiovy Gory MSU, Moscow, 119899, Russia

    Andre Kamkin

  2. , Fundamental and Applied Physiology, Russian State Medical University, Ostrovitjanova Str 1, Moscow, 117997, Russia

    Ilya Lozinsky

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© 2012 Springer Science+Business Media Dordrecht

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Suzuki, M., Mizuno, A. (2012). The Molecular Mechanism of Multifunctional Mechano-Gated Channel TRPV4. In: Kamkin, A., Lozinsky, I. (eds) Mechanically Gated Channels and their Regulation. Mechanosensitivity in Cells and Tissues, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5073-9_4

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