Impairment of proprioceptive movement and mechanical nociception in Drosophila melanogaster larvae lacking Ppk30, a Drosophila member of the Degenerin/Epithelial Sodium Channel family

Abstract

The mechanosensory neurons of Drosophila larvae are demonstrably activated by diverse mechanical stimuli, but the mechanisms underlying this function are not completely understood. Here we report a genetic, immunohistochemical, and electrophysiological analysis of the Ppk30 ion channel, a member of the Drosophila pickpocket (ppk) family, counterpart of the mammalian Degenerin/Epithelial Na+ Channel family. Ppk30 mutant larvae displayed deficits in proprioceptive movement and mechanical nociception, which are detected by class IV sensory (mdIV) neurons. The same neurons also detect heat nociception, which was not impaired in ppk30 mutant larvae. Similarly, Ppk30 mutation did not alter gentle touch mechanosensation, a distinct mechanosensation detected by other neurons, suggesting that Ppk30 has a functional role in mechanosensation in mdIV neurons. Consistently, Ppk30 was expressed in class IV neurons, but was not detectable in other larval skin sensory neurons. Mutant phenotypes were rescued by expressing Ppk30 in mdIV neurons. Electrophysiological analysis of heterologous cells expressing Ppk30 did not detect mechanosensitive channel activities, but did detect acid‐induced currents. These data show that Ppk30 has a role in mechanosensation, but not in thermosensation, in class IV neurons, and possibly has other functions related to acid response.

Structural and transcriptional evidence of mechanotransduction in the Drosophila suzukii ovipositor

“…We specifically looked for contigs orthologous to mechanosensitive genes described so far in D. melanogaster (Karkali and Martin-Blanco, 2017): the putative metazoan mechanotransduction channels, i.e. degenerin/epithelial Na + channel C (DeG/eNaC) (Adams et al, 1998;Gorczyca et al, 2014;Guo et al, 2014;Jang et al, 2019;Tsubouchi et al, 2012;Zhong et al, 2010), the transient receptor potential (TRP) channels (Cheng et al, 2010;Gong et al, 2004;Göpfert et al, 2006;Tracey et al, 2003;Tsubouchi et al, 2012;Walker et al, 2000), the two-pore domain K + channel proteins (K2P) (Tabarean and Morris, 2002), as well as piezo (Kim et al, 2012), piezo-like (pzl) (Hu et al, 2019) and transmembrane channel-like (tmc) genes (Guo et al, 2016).…”

“…Among genes whose expression is completely shared among the four species there are three DeG/eNaC proteins (which in Drosophila are commonly referred to as pickpocket proteins): ppk, rpk, and ppk26 (Adams et al, 1998;Gorczyca et al, 2014;Tsubouchi et al, 2012;Zhong et al, 2010). Only transcripts encoding a fourth pickpocket protein (ppk30), which has been recently related to mechanotransduction in D. melanogaster (Jang et al, 2019), are absent in all samples. Also piezo, its paralog pzl, as well as shaker and painless (pain) have a presence-absence pattern conserved across species.…”

Drosophila as a Model to Study the Mechanism of Nociception

“…Ppk1 and ppk26 have the same signaling pathway to regulate mechanical nociception, and they do not have functional response to in thermal stimulus ( Gorczyca et al, 2014 ). Ppk30 as a member of the Drosophila Ppk family is detected by class IV multidendritic neurons, and has a role in mechanosensation, but not in thermosensation ( Jang et al, 2019 ).…”

Drosophila ppk19 encodes a proton-gated and mechanosensitive ion channel

“…Phylogenetic analysis revealed that Ppk19 belongs to the subfamily that includes Ppk30 (Fig. 1 A), which was previously shown to be required for mechanical nociception and larval movement 11 . This prompted us to examine whether Ppk19 might form ion channels with functions similar to those of Ppk30.…”

“…Proteins of the Ppk family (and the broader Deg/ENaC family) function as homotrimers or heterotrimers, suggesting there may be additional Ppk channels involved in mechanosensation in mdIV neurons. Genetic analysis identified Ppk26 and Ppk30 as also expressed in mdIV neurons, and furthermore that they have roles identical to Ppk1 with respect to mechanosensation 8 – 11 . Here we identify Ppk19 as a new family member dedicated to mechanosensation in mdIV neurons.…”