title: A presynaptic ENaC channel drives homeostatic plasticity.
abstract: An electrophysiology-based forward genetic screen has identified two genes, pickpocket11 (ppk11) and pickpocket16 (ppk16), as being necessary for the homeostatic modulation of presynaptic neurotransmitter release at the Drosophila neuromuscular junction (NMJ). Pickpocket genes encode Degenerin/Epithelial Sodium channel subunits (DEG/ENaC). We demonstrate that ppk11 and ppk16 are necessary in presynaptic motoneurons for both the acute induction and long-term maintenance of synaptic homeostasis. We show that ppk11 and ppk16 are cotranscribed as a single mRNA that is upregulated during homeostatic plasticity. Acute pharmacological inhibition of a PPK11- and PPK16-containing channel abolishes the expression of short- and long-term homeostatic plasticity without altering baseline presynaptic neurotransmitter release, indicating remarkable specificity for homeostatic plasticity rather than NMJ development. Finally, presynaptic calcium imaging experiments support a model in which a PPK11- and PPK16-containing DEG/ENaC channel modulates presynaptic membrane voltage and, thereby, controls calcium channel activity to homeostatically regulate neurotransmitter release.
authors: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-0822, USA.
authors: Meg A
authors: MA
authors: Younger
authors: Martin
authors: M
authors: Müller
authors: Amy
authors: A
authors: Tong
authors: Edward C
authors: EC
authors: Pym
authors: Graeme W
authors: GW
authors: Davis
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism; D002490:Central Nervous System / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D007814:Larva; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D015222:Sodium Channels / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D053503:Epithelial Sodium Channels; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D018733:Nicotinic Antagonists; D011073:Polyamines; D015222:Sodium Channels; C532965:ppk protein, Drosophila; C013407:benzamil; C034092:delta-philanthotoxin; D000584:Amiloride; D002118:Calcium; C039614:ethylisopropylamiloride
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