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Review
. 2024 Oct 29;24(21):6923.
doi: 10.3390/s24216923.

TRPV4-A Multifunctional Cellular Sensor Protein with Therapeutic Potential

Sanna Koskimäki  1 , Sari Tojkander  1
Affiliations
Review

TRPV4-A Multifunctional Cellular Sensor Protein with Therapeutic Potential

Sanna Koskimäki et al. Sensors (Basel). .

Abstract

Transient receptor potential vanilloid (TRPV) channel proteins belong to the superfamily of TRP proteins that form cationic channels in the animal cell membranes. These proteins have various subtype-specific functions, serving, for example, as sensors for pain, pressure, pH, and mechanical extracellular stimuli. The sensing of extracellular cues by TRPV4 triggers Ca2+-influx through the channel, subsequently coordinating numerous intracellular signaling cascades in a spatio-temporal manner. As TRPV channels play such a wide role in various cellular and physiological functions, loss or impaired TRPV protein activity naturally contributes to many pathophysiological processes. This review concentrates on the known functions of TRPV4 sensor proteins and their potential as a therapeutic target.

Keywords: TRP channels; TRPV; TRPV4; mechanotransduction; sensors; therapeutic targeting.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
TRPV4 channel in the maintenance of epithelial integrity. (A) Spatially and temporally very strictly controlled ion influx through TRPV4 channel in response to several extracellular cues affects various cellular processes through its impact on intracellular cascades. One of these TRPV4-dependent functions is the maintenance of epithelial integrity through the control of actomyosin assembly. (B) TRPV4 dysfunction, namely over- or under-expression, can, therefore, have a major impact on the cellular functions within different tissue types through the disturbance in normal calcium influx. (C) In epithelial sheets, TRPV4 takes part in the control of intact epithelial junctions, maintaining epithelial integrity and permeability. This takes place at least through its impact on junctional proteins and actomyosin contractility, which is important for junctional force production. TRPV4 can regulate actomyosin contractility at least through the Ca2+/Calmodulin pathway and Rho kinases (D) Loss of TRPV4 from the epithelial cell populations subsequently leads to disrupted cellular features and impaired epithelial integrity, leading to mesenchymal cell types.
Figure 2
Figure 2
TRPV4 acts as an essential sensor of extracellular cues, such as mechanical stimuli, osmotic pressure, and temperature. Spatio-temporal activation of TRPV4 by these various cues leads to activation of intracellular signaling cascades through controlled calcium influx, therefore impacting several cellular events and homeostasis of distinct tissues. Altered TRPV4 activity is consequently associated with a number of pathophysiological conditions through deregulation of cellular functions.
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