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.

Keywords: Cryo-electron microscopy; PKD1; PKD2; Polycystin; TRPA; TRPC; TRPM; TRPML; TRPP; TRPV; Thermosensation; Transient receptor potential channels.

Fig. 6.1

A schematic representation of the TRP superfamily of ion channels. Each branching group is representative of a subfamily of channels

Fig. 6.2

Select high resolution structures of TRP channels. (a) and (b) Cryo-EM density maps of TRPV1 (Liao et al. 2013; Gao et al. 2016). (c) and (d) Cryo-EM density maps of TRPV2 (Huynh et al. 2016; Zubcevic et al. 2016). (e) X-ray crystal structure of TRPV6 (Saotome et al. 2016). (f) Cryo-EM density map of TRPA1 (Paulsen et al. 2015). (g) and (h) Cryo-EM density maps of TRPP2 (Grieben et al. 2016; Shen et al. 2016)

Fig. 6.3

A schematic representation of the the TRP channel pore showing the two regions of constriction (gates). The residues forming the two gates in various TRP proteins are listed in the Table on the right

Fig. 6.4

A schematic representation of TRPP1 and TRPP2 interacting with each other through their C-terminal region and forming the receptor-channel complex