Identification of Ppk26, a DEG/ENaC Channel Functioning with Ppk1 in a Mutually Dependent Manner to Guide Locomotion Behavior in Drosophila

Abstract

Summary A major gap in our understanding of sensation is how a single sensory neuron can differentially respond to a multitude of different stimuli (polymodality), such as propio- or noci- sensation. The prevailing hypothesis is that different stimuli are transduced through ion channels with diverse properties and subunit composition. In a screen for ion channel genes expressed in polymodal nociceptive neurons we identified Ppk26, a member of the trimeric Degenerin/Epithelial Sodium (DEG/ENaC) channel family as being necessary for proper locomotion behavior in Drosophila larvae in a mutually dependent fashion with co-expressed Ppk1, another member of the same family. Mutants lacking Ppk1 and Ppk26 were defective in mechanical but not thermal nociception behavior. Mutants of Piezo, a channel involved in mechanical nociception in the same neurons, did not show a defect in locomotion, suggesting distinct molecular machinery for mediating locomotor feedback and mechanical nociception.

Transmembrane channel-like ( tmc ) gene regulates Drosophila larval locomotion

“…It is reported that NOMPC is expressed in class I da neurons and bd neurons, and mutations of NOMPC cause prolonged stride duration and reduced crawling speed of mutant larvae (9). In contrast, the DEG/ ENaC ion channels PPK and PPK26 function in class IV da neurons to modulate the extent of linear locomotion; reduction of these channel functions leads to decreased turning frequency and enhanced directional crawling (6,10).…”

“…The TRPN channel NOMPC functions in class III da neurons to mediate gentle touch sensation (13) whereas the DEG/ENaC ion channels PPK and PPK26, the TRP channel Painless, and Piezo function in class IV da neurons to mediate mechanical nociception (10,20,(46)(47)(48). As to proprioception, chordotonal organs, class I and class IV da neurons and bd neurons may all contribute to proprioception to regulate larval locomotion behavior (5)(6)(7)(8)10). It is reported that NOMPC is expressed in class I da neurons and bd neurons, and mutations of NOMPC cause prolonged stride duration and reduced crawling speed of mutant larvae (9).…”

“…The locomotion assay was performed similarly as previously described (5,10). Videotaped locomotion behavior was analyzed offline using the Noldus software.…”

“…It has been known for centuries that proprioception is mediated by mechanosensitive proprioceptors (1,3) such as mammalian muscle spindles and Golgi tendon organs (2,3). In insects, mechanosensory campaniform sensilla, trichoform sensilla, chordotonal organs, and stretch receptors reportedly serve proprioceptive roles (4)(5)(6)(7)(8)(9)(10).…”

“…The molecular mechanisms underlying proprioceptive transduction have just begun to be elucidated. Among mechanosensitive ion channel candidates such as certain members of the transient receptor potential (TRP) channels (12)(13)(14), degenerin/epithelial sodium channels (DEG/ENaC) (15)(16)(17), Piezo (18)(19)(20), transmembrane channel-like (TMC) (21), K2P (22)(23)(24), and MscL (large-conductance mechanosensitive channel) (24,25), TRPN and DEG/ENaC ion channels have been proposed to be mechanosensitive ion channels involved in proprioception in nematodes (26,27), fruit flies (6,9,10) and zebrafish (28). Recently, it was reported that Piezo2 is essential for the mechanosensitivity of mammalian proprioceptors (29).…”