title: 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 flyDrosophila melanogasteris an excellent model for deciphering the functions of DEG/ENaC genes because its genome encodes an exceptionally large number of DEG/ENaC subunits termedpickpocket(ppk)1-31Here we demonstrate thatppk29contributes specifically to the postsynaptic modulation of excitatory synaptic transmission at the larval neuromuscular junction. Electrophysiological data indicate that the function ofppk29in muscle is necessary for normal postsynaptic responsivity to neurotransmitter release and for normal coordinated larval movement. Theppk29mutation 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 STATEMENTMembers 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 ofDrosophilagenetics in combination with electrophysiological and behavioral approaches, we demonstrate that the DEG/ENaC-encoding genepickpocket 29contributes to baseline neurotransmission, possibly via the modulation of postsynaptic glutamate receptor functionality.
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130.
authors.forename: Alexis
authors.identifier: 0000-0003-1715-4615
authors.initials: A
authors.lastname: Hill
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130.|Donald Danforth Plant Science Center, St. Louis, Missouri 63132, and.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Neurobiology, University of Southern California, Los Angeles, California 90089.
authors.forename: Xiling
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130.
authors.forename: Ross
authors.identifier: 0000-0001-5387-6266
authors.initials: R
authors.lastname: McKinney
authors.affiliation: Department of Neurobiology, University of Southern California, Los Angeles, California 90089.
authors.forename: Dion
authors.identifier: 0000-0003-1884-284X
authors.initials: D
authors.lastname: Dickman
authors.affiliation: Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, benshahary@wustl.edu.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Ben-Shahar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D062626:Degenerin Sodium Channels / Q000502:physiology; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D053503:Epithelial Sodium Channels / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D062626:Degenerin Sodium Channels; D029721:Drosophila Proteins; D053503:Epithelial Sodium Channels; D007473:Ion Channels; C573946:PPK29 protein, Drosophila; D012964:Sodium
keywords: DEG/ENaC; Drosophila melanogaster; NMJ; fruit fly; synapse