The Drosophila Postsynaptic DEG/ENaC Channel ppk29 Contributes to Excitatory Neurotransmission

J Neurosci. 2017 Mar 22;37(12):3171-3180. doi: 10.1523/JNEUROSCI.3850-16.2017. Epub 2017 Feb 17.


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.SIGNIFICANCE STATEMENT Members of the degenerin/epithelial sodium channel (DEG/ENaC) family are broadly expressed in epithelial and neuronal tissues. To date, the neurophysiological functions of most family members remain unknown. Here, by using the power of Drosophila genetics in combination with electrophysiological and behavioral approaches, we demonstrate that the DEG/ENaC-encoding gene pickpocket 29 contributes to baseline neurotransmission, possibly via the modulation of postsynaptic glutamate receptor functionality.

Keywords: DEG/ENaC; Drosophila melanogaster; NMJ; fruit fly; synapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Degenerin Sodium Channels / physiology
  • Drosophila / physiology*
  • Drosophila Proteins / physiology*
  • Epithelial Sodium Channels / physiology
  • Excitatory Postsynaptic Potentials / physiology*
  • Ion Channel Gating / physiology*
  • Ion Channels / physiology*
  • Neuromuscular Junction / physiology*
  • Sodium / metabolism*
  • Synaptic Transmission / physiology


  • Degenerin Sodium Channels
  • Drosophila Proteins
  • Epithelial Sodium Channels
  • Ion Channels
  • PPK29 protein, Drosophila
  • Sodium