Transient receptor potential (TRP) ion channels are emerging as a new set of membrane proteins involved in a vast array of cellular processes and regulated by a large number of physical and chemical stimuli, which involves them with sensory cell physiology. The vanilloid TRP subfamily (TRPV) named after the vanilloid receptor 1 (TRPV1) consists of six members, and at least four of them (TRPV1–TRPV4) have been related to thermal sensation. One of the least characterized members of the TRP subfamily is TRPV2. Although initially characterized as a noxious heat sensor, TRPV2 now seems to have little to do with temperature sensing but a much more complex physiological profile. Here we review the available information and research progress on the structure, physiology and pharmacology of TRPV2 in an attempt to shed some light on the physiological and pharmacological deorphanization of TRPV2.

Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca²⁺ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca²⁺ influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity.

TRPV4 cation channel activation by cytochrome P450-mediated derivatives of arachidonic acid (AA), epoxyeicosatrienoic acids (EETs), constitute a major mechanisms of endothelium-derived vasodilatation. Besides, TRPV4 mechano/osmosensitivity depends on phospholipase A₂(PLA₂) activation and subsequent production of AA and EETs. However, the lack of evidence for a direct interaction of EETs with TRPV4 together with claims of EET-independent mechanical activation of TRPV4 has cast doubts on the validity of this mechanism. We now report: 1) The identification of an EET-binding pocket that specifically mediates TRPV4 activation by 5′,6′-EET, AA and hypotonic cell swelling, thereby suggesting that all these stimuli shared a common structural target within the TRPV4 channel; and 2) A structural insight into the gating of TRPV4 by a natural agonist (5′,6′-EET) in which K535 plays a crucial role, as mutant TRPV4-K535A losses binding of and gating by EET, without affecting GSK1016790A, 4α-phorbol 12,13-didecanoate and heat mediated channel activation. Together, our data demonstrates that the mechano- and osmotransducing messenger EET gates TRPV4 by a direct action on a site formed by residues from the S2-S3 linker, S4 and S4-S5 linker.

Piezo1 transduces mechanical forces at the intercellular bridge to coordinate the machinery necessary to split dividing cells.

The transient receptor potential vanilloid family includes four ion channels–TRPV1, TRPV2, TRPV3 and TRPV4–that are represented within the vertebrate subphylum and involved in several sensory and physiological processes. These channels are related to adaptation to the environment, and probably under strong evolutionary pressure. Using multiple sequence alignments as source for evolutionary, bioinformatics and statistical analysis, we have analyzed the evolutionary profiles for TRPV1, TRPV2, TRPV3 and TRPV4. The evolutionary pressure exerted over vertebrate TRPV2 sequences compared to the other channels argues for a positive selection profile for TRPV2 compared to TRPV1, TRPV3 and TRPV4. We have analyzed the selective pressure on specific protein domains, observing a common selective pressure trend for the common TRPV scaffold, consisting of the ankyrin repeat domain, the membrane proximal domain, the transmembrane domain, and the TRP domain. Through a more detailed analysis we have identified evolutionary constraints involved in the subunit contact at the transmembrane domain level. Performing evolutionary comparison, we have translated specific channel structural information such as the transmembrane topology, and the interaction between the membrane proximal domain and the TRP box. We have also identified potential common regulatory domains among all TRPV1-4 members, such as protein-protein, lipid-protein and vesicle trafficking domains.

A TRPV2 interactome-based signature for prognosis in glioblastoma patients A TRPV2 interactome-based signature for prognosis in glioblastoma patients