Transient Receptor Potential Cation Channel Subfamily Vanilloid Member 3 is not Involved in Plasma Membrane Stretch-induced Intracellular Calcium Signaling in Merkel Cells

Higashikawa, Asuka; Kojima, Yoshiyuki; Sato, Masaki; Kimura, Masashi; Ogura, Kazuhiro; Mochizuki, Hideki; Sase, Toshiyuki; Shinya, Akinori; Kobune, Kunio; Furuya, Tadashi; Satô, Tôru; Shibukawa, Yoshiyuki; Tazaki, Masakazu

doi:10.2209/tdcpublication.56.259

Cited by 3 publications

(2 citation statements)

References 6 publications

(9 reference statements)

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“…Synthetic and natural compounds, like isopentenyl pyrophosphate (Bang et al, 2011), 17(R)-resolvin D1 (Bang et al, 2012), forsythoside B (Zhang et al, 2019), diphenyltetrahydrofuran osthole (Higashikawa et al, 2015) and ruthenium red (Xu et al, 2002) have been proposed to inhibit TRPV3 channels. Due to either or both the lack of targeting specificity and the clinical application, their remedial potential remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

Yao

Liu

et al. 2020

Preprint

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The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is selectively targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular docking and mutagenesis, we further uncovered single residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.

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Section: Discussionmentioning

confidence: 99%

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

Yao

Liu

et al. 2020

Preprint

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“…for the role of TRPV3 or TRPV5 in the mechanotransduction. Additionally, in the study by Higashikawa et al, TRPV3 was not found to be stimulated by mechanical stretching [202]. It has, however, been shown that TRPV3 forms a signaling complex with TGF-α and EGFR and that this complex plays a role in the mechanical skin barrier function [203].…”

Section: Are All the Trpv Channels Mechanosensitive?mentioning

confidence: 98%

TRPV Protein Family—From Mechanosensing to Cancer Invasion

Kärki

Tojkander

2021

Biomolecules

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Biophysical cues from the cellular microenvironment are detected by mechanosensitive machineries that translate physical signals into biochemical signaling cascades. At the crossroads of extracellular space and cell interior are located several ion channel families, including TRP family proteins, that are triggered by mechanical stimuli and drive intracellular signaling pathways through spatio-temporally controlled Ca2+-influx. Mechanosensitive Ca2+-channels, therefore, act as critical components in the rapid transmission of physical signals into biologically compatible information to impact crucial processes during development, morphogenesis and regeneration. Given the mechanosensitive nature of many of the TRP family channels, they must also respond to the biophysical changes along the development of several pathophysiological conditions and have also been linked to cancer progression. In this review, we will focus on the TRPV, vanilloid family of TRP proteins, and their connection to cancer progression through their mechanosensitive nature.

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Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

Liu

Wang

Wei

et al. 2021

eLife

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The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular simulations and mutagenesis, we further uncovered key residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.

show abstract

Transient Receptor Potential Cation Channel Subfamily Vanilloid Member 3 is not Involved in Plasma Membrane Stretch-induced Intracellular Calcium Signaling in Merkel Cells

Cited by 3 publications

References 6 publications

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

TRPV Protein Family—From Mechanosensing to Cancer Invasion

Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine

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