TheDrosophilaPostsynaptic DEG/ENaC Channelppk29Contributes to Excitatory Neurotransmission

Abstract

The protein family of degenerin/epithelial sodium channels (DEG/ENaCs) is composed of diverse animal-specific, non-voltage-gated ion channels that play important roles in regulating cationic gradients across epithelial barriers. Some family members are also enriched in neural tissues in both vertebrates and invertebrates. However, the specific neurophysiological functions of most DEG/ENaC-encoding genes remain poorly understood. The fruit fly Drosophila melanogaster is an excellent model for deciphering the functions of DEG/ENaC genes because its genome encodes an exceptionally large number of DEG/ENaC subunits termed pickpocket (ppk) 1-31. Here we demonstrate that ppk29 contributes specifically to the postsynaptic modulation of excitatory synaptic transmission at the larval neuromuscular junction. Electrophysiological data indicate that the function of ppk29 in muscle is necessary for normal postsynaptic responsivity to neurotransmitter release and for normal coordinated larval movement. The ppk29 mutation does not affect gross synaptic morphology and ultrastructure, which indicates that the observed phenotypes are likely due to defects in glutamate receptor function. Together, our data indicate that DEG/ENaC ion channels play a fundamental role in the postsynaptic regulation of excitatory neurotransmission.

Composition and Control of a Deg/ENaC Channel during Presynaptic Homeostatic Plasticity

“…In this experiment, PPK1 puncta can be clearly observed in the motoneuron cell body and presynaptic boutons (Figure 6B). However, PPK1 staining in the trachea and muscle overlap with the NMJ, making it difficult to clearly asses protein distribution at the NMJ, consistent with the existence of other PPK subunits expressed in muscle (Hill et al, 2017). Therefore, we over-expressed UAS-ppk1 -GFP presynaptically ( C155-GAL4 ) in the ppk LR mutant background and stained with the anti-GFP antibody to increase signal intensity.…”

Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes

“…However, ASICs are widely distributed in the vertebrate nervous system and contribute to behaviors that are conserved across most animals, including nociception, chemosensation, and mechanosensation (11,12). Furthermore, ASICs derive from the degenerin/epithelial Na + channel (DEG/ENaC) family, genes of which are conserved throughout all major animal lineages (3), and some of which are expressed in invertebrate postsynaptic membranes (13). These facts are difficult to reconcile with ASICs being limited to the jawed vertebrates.…”

Unforgettable force – crosstalk and memory of mechanosensitive structures

“…The potassium channels TREKs and TRAAK, for instance, adjust the potential for hyperpolarization in neurons and thereby counteract the activity of non-selective Piezo channels (Brohawn et al, 2014a(Brohawn et al, ,2014bBrohawn, 2015). ENaC calcium channels can initiate neurotransmitter release at the synapse (Hill et al, 2017), while Piezo-mediated calcium influxes can induce very specific cell type-dependent responses, such as stimulating transglutaminase activity in myocytes to induce the constriction of small blood vessels (Retailleau et al, 2015). As acute changes in ion concentrations, especially Ca 2+ levels, affect a whole range of intracellular signaling cascades, MS ion channels impact cellular behavior in the short-term (Doyle et al, 2004), but can also lead to long-lasting changes in gene transcription activities (Berridge et al, 2003).…”