A Comparative Perspective on Functionally-Related, Intracellular Calcium Channels: The Insect Ryanodine and Inositol 1,4,5-Trisphosphate Receptors

Abstract

Calcium (Ca²⁺) homeostasis is vital for insect development and metabolism, and the endoplasmic reticulum (ER) is a major intracellular reservoir for Ca²⁺. The inositol 1,4,5- triphosphate receptor (IP₃R) and ryanodine receptor (RyR) are large homotetrameric channels associated with the ER and serve as two major actors in ER-derived Ca²⁺ supply. Most of the knowledge on these receptors derives from mammalian systems that possess three genes for each receptor. These studies have inspired work on synonymous receptors in insects, which encode a single IP₃R and RyR. In the current review, we focus on a fundamental, common question: "why do insect cells possess two Ca²⁺ channel receptors in the ER?". Through a comparative approach, this review covers the discovery of RyRs and IP₃Rs, examines their structures/functions, the pathways that they interact with, and their potential as target sites in pest control. Although insects RyRs and IP₃Rs share structural similarities, they are phylogenetically distinct, have their own structural organization, regulatory mechanisms, and expression patterns, which explains their functional distinction. Nevertheless, both have great potential as target sites in pest control, with RyRs currently being targeted by commercial insecticide, the diamides.

Keywords: calcium channel; diamide; endoplasmic reticulum; inositol 1,4,5-trisphosphate receptor; pest control; ryanodine receptor.

Figure 1

The conserved domains for RyR are listed as following MIR (Mannosyltransferase, IP₃R, and RyR, pfam02815), RIH (RyR and IP₃R Homology, pfam01365), the SPRY (spIA and RyR domains, pfam00622), RyR domain (pfam02026) [71,90,91,92], RIH A domains (RIH-associated, pfam08454) [89], EF-hands, and putative transmembrane domain (TM1-TM6). IP₃R has three putative functional regions: ligand binding, central regulatory, and channel forming sites. Ligand binding region includes three subdomains, the IP₃-binding core β (IBC-β) and α (IBC-α) that interact with IP₃; and the suppressor domain (SD) reducing the affinity for IP₃ [81,82,83,84,85]. The conserved domains for IP₃R are listed as following MIR RIH, RIH A, and TM1-TM6. Arrow corresponding to TM5 and TM6 including the suppressor domain and ligand binding, which leads to modulation of the gating of the Ca²⁺ pore in both channels.

Figure 2

Phylogenetic analysis tree of IP₃R and RyR, constructed by aligning amino acid sequences from representative species of animal phyla using the MUSCLE algorithm of MEGA-X software, version 10.0 (www.megasoftware.net) (accessed on 21 March 2021) [133]. Phylogenetic trees were constructed by using the maximum likelihood method and Le Gascuel model [134]. The bootstrap consensus tree inferred from 1000 replicates is taken to represent the evolutionary history of the taxa analyzed [135]. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates were collapsed. Representative proteins and their accession numbers are given in Supplementary Table S1.