TRPV3: time to decipher a poorly understood family member!

Abstract

The vanilloid transient receptor potential channel TRPV3 differs in several aspects from other members of the TRPV subfamily. This Ca(2+)-, ATP- and calmodulin-regulated channel constitutes a target for many natural compounds and has a unique expression pattern as the most prominent and important TRP channel in keratinocytes of the skin. Although TRPV3 is considered as a thermosensitive channel, its function as a thermosensor in the skin is challenged. Nevertheless, it plays important roles in other skin functions such as cutaneous sensations, hair development and barrier function. More recently, mutations in TRPV3 were linked with a rare genodermatosis known as the Olmsted syndrome. This review gives an overview on properties of TRPV3 and its functions in the skin and skin diseases.

Figure 1

TRPV3 is a member of the vanilloid subfamily of TRP channels A, phylogenetic relationship between TRPV channels. B, cryoelectron microscopy structure of the TRPV1 channel (Moiseenkova-Bell et al. 2011). Docking of the high-resolution structure of Kv1.2 transmembrane domains (maroon; PDB entry 2A79) and TRPV1 ankyrin domains (green; PDB entry 2PNN; two of four such domains are shown) into the TRPV1 three-dimensional reconstruction (adapted, with permission, from Moiseenkova-Bell et al. 2011).

Figure 2

Predicted structural topology of TRPV3 A, localization of major functional domains and residues in TRPV3. Residues involved in heat activation (Ile644, Asn647 and Tyr661), activation by 2-APB (His426 and Arg696), and calcium sensitivity (Arg696) as well as the extracellular site Asp641 are indicated. B, ARD of TRPV3 shows an insertion and two deletions (indicated by green and blue, respectively) when compared with the TRPV1-ARD structure. ATP binding sites with docked ATP are coloured purple, between AR2 and AR3, established by K169, K174, L177, Y213, Q216, I221 and E224 (adapted, with permission, from Phelps et al. 2012).

Figure 3

Missense mutations in TRPV3 are involved in the Olmsted syndrome A, linear representation of TRPV3 with annotations of OLM mutations. B, transgenic mouse with the G573S mutation (right) shows hyperkeratosis and thickening of the back skin when compared with the control DS animals (left; reproduced, with permission, from Yoshioka et al. 2002). C, keratoderma involving most of the palmar and plantar aspects in a 12-year-old boy with the Olmsted syndrome (reproduced, with permission, from Lai-Cheong et al. 2013).