Transient Receptor Potential (TRP) Channels

Abstract

Transient Receptor Potential (TRP) channels are evolutionarily conserved integral membrane proteins. The mammalian TRP superfamily of ion channels consists of 28 cation permeable channels that are grouped into six subfamilies based on sequence homology (Fig. 6.1). The canonical TRP (TRPC) subfamily is known for containing the founding member of mammalian TRP channels. The vanilloid TRP (TRPV) subfamily has been extensively studied due to the heat sensitivity of its founding member. The melastatin-related TRP (TRPM) subfamily includes some of the few known bi-functional ion channels, which contain functional enzymatic domains. The ankyrin TRP (TRPA) subfamily consists of a single chemo-nociceptor that has been proposed to be a target for analgesics. The mucolipin TRP (TRPML) subfamily channels are found primarily in intracellular compartments and were discovered based on their critical role in type IV mucolipidosis (ML-IV). The polycystic TRP (TRPP) subfamily is a diverse group of proteins implicated in autosomal dominant polycystic kidney disease (ADPKD). Overall, this superfamily of channels is involved in a vast array of physiological and pathophysiological processes making the study of these channels imperative to our understanding of subcellular biochemistry.

Phylogenetic inference identifies two eumetazoan TRPM clades and an 8th family of TRP channel, TRP soromelastatin (TRPS)

“…The vertebrate TRPM1-8 expansion has been the focus of the majority of TRPM literature, and has been the principal basis for characterizing TRPM channels (Samanta, et al 2018; Zhang, et al 2018; Chen, et al 2019). However, these trees evidence that the TRPM1-8 expansion occurred after the vertebrate-tunicate split, and before agnathans (jawless fish; lampreys and hagfish) split from the ancestor of all other vertebrates ( Fig.…”

“…While some have been careful in describing TRP channels in taxon-specific ways (Saito and Shingai 2006; Hofmann, et al 2010; Peng, et al 2015), these findings are the strongest challenge to the pervasive, vertebrate-centric dogma that the TRPM family is constituted by 8 distinct paralogues organized into four subfamilies (Samanta, et al 2018; Zhang, et al 2018; Chen, et al 2019). These results instead support that the eumetazoan TRPM family consists of two distinct radiations (αTRPM and βTRPM) which themselves predate the Cnidaria-Bilateria split.…”

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

“…As mentioned above, TRP channels are widely expressed in almost every mammalian cell, predominantly in the brain. TRP channels can be activated by diverse stimuli ranging from temperature, mechanical or osmotic stress, chemical compounds, and redox modification (Sawamura et al, 2017;Samanta et al, 2018). Based on sequence homology, the TRP superfamily is divided into six subfamilies in mammals: TRPC (classical or canonical; seven sub-members), TRPM (melastatin; eight submembers), TRPV (vanilloid; six sub-members), TRPA (ankyrin; one sub-member), TRPP (polycystin; three sub-members), and TRPML (mucolipin; three sub-members) (Figure 1).…”

Peripheral Sensitization

“…The TRPV is one of the subfamilies of the transient receptor potential (TRP) through which the external stimuli are transduced to electrical impulses. Based on amino acid sequence homology, members of this family in the mammalian have been classified into six subfamilies: TRPA (ankyrin), TRPV (vanilloid), TRPM (melastatin), TRPC (canonical), TRPP (polycystin), and TRPML (mucolipin) [41]. TRP channels are tetramers composed of identical subunits, which have six transmembrane domains and cytoplasmic amino and carboxy termini [42].…”