Abstract
ThermoTRP channels (thermoTRPs) define a subfamily of the transient receptor potential (TRP) channels that are activated by changes in the environmental temperature, from noxious cold to injurious heat. Acting as integrators of several stimuli and signalling pathways, dysfunction of these channels contributes to several pathological states. The surface expression of thermoTRPs is controlled by both, the constitutive and regulated vesicular trafficking. Modulation of receptor surface density during pathological processes is nowadays considered as an interesting therapeutic approach for management of diseases, such as chronic pain, in which an increased trafficking is associated with the pathological state. This review will focus on the recent advances trafficking of the thermoTRP channels, TRPV1, TRPV2, TRPV4, TRPM3, TRPM8 and TRPA1, into/from the plasma membrane. Particularly, regulated membrane insertion of thermoTRPs channels contributes to a fine tuning of final channel activity, and indeed, it has resulted in the development of novel therapeutic approaches with successful clinical results such as disruption of SNARE-dependent exocytosis by botulinum toxin or botulinomimetic peptides.
Highlights
Transient receptor potential (TRP) channels consist of a large family of ion channels that play a wide diversity of physiological functions [1,2,3]
Thermosensory channels, named “thermoTRPs”, define a subfamily of the transient receptor potential (TRP) channels that are activated by changes in the environmental temperature, from noxious cold (42 °C) (Figure 1)
TRPA1 was initially suggested to function as a detector of noxious cold, less than 17 °C [3,201], and to account for a component of cold sensitivity not mediated by transient receptor potential melastatin 8 (TRPM8) [189]
Summary
Transient receptor potential (TRP) channels consist of a large family of ion channels that play a wide diversity of physiological functions [1,2,3]. Acting as integrators of several stimuli and signalling pathways, dysfunction of these channels, for instance, contributes to thermal hyperalgesia and allodynia under pathological painful conditions such as inflammation or cancer [4,5,6,7]. For this reason, thermoTRPs have become pivotal drug targets, and the development of therapeutic compounds for pharmacological intervention is actively pursued by the academy and the industry [8,9]. The clear contribution of this mechanism to the final channel function has opened exciting research lines driven to the development of novel therapeutic approaches with successful clinical results in the treatment of several painful pathologies
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