title: Regulation of synaptic development and function by the Drosophila PDZ protein Dyschronic.
abstract: Synaptic scaffold proteins control the localization of ion channels and receptors, and facilitate molecular associations between signaling components that modulate synaptic transmission and plasticity. Here, we define novel roles for a recently described scaffold protein, Dsychronic (DYSC), at the Drosophila larval neuromuscular junction. DYSC is the Drosophila homolog of whirlin/DFNB31, a PDZ domain protein linked to Usher syndrome, the most common form of human deaf-blindness. We show that DYSC is expressed presynaptically and is often localized adjacent to the active zone, the site of neurotransmitter release. Loss of DYSC results in marked alterations in synaptic morphology and cytoskeletal organization. Moreover, active zones are frequently enlarged and misshapen in dysc mutants. Electrophysiological analyses further demonstrate that dysc mutants exhibit substantial increases in both evoked and spontaneous synaptic transmission. We have previously shown that DYSC binds to and regulates the expression of the Slowpoke (SLO) BK potassium channel. Consistent with this, slo mutant larvae exhibit similar alterations in synapse morphology, active zone size and neurotransmission, and simultaneous loss of dysc and slo does not enhance these phenotypes, suggesting that dysc and slo act in a common genetic pathway to modulate synaptic development and output. Our data expand our understanding of the neuronal functions of DYSC and uncover non-canonical roles for the SLO potassium channel at Drosophila synapses.
authors.affiliation: Department of Neuroscience, The Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA UCL Institute of Neurology, London WC1N 3BG, UK.
authors.forename: James E C
authors.initials: JE
authors.lastname: Jepson
authors.affiliation: Department of Neuroscience, The Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shahidullah
authors.affiliation: Department of Neuroscience, The Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Die
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, The Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Sylvain J
authors.initials: SJ
authors.lastname: le Marchand
authors.affiliation: Department of Neurology, John Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurology, John Hopkins University, Baltimore, MD 21287, USA.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Wu
authors.affiliation: Department of Neuroscience, The Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Irwin B
authors.initials: IB
authors.lastname: Levitan
authors.affiliation: Department of Neuroscience, The Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dalva
authors.affiliation: Department of Neuroscience, The Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA kyunghee.koh@jefferson.edu.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Koh
mesh_terms: D000818:Animals; D004330:Drosophila / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D007814:Larva / Q000254:growth & development; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D009469:Neuromuscular Junction / Q000254:growth & development*; D054731:PDZ Domains / Q000235:genetics; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
chemical_list: C000594662:DYSC protein, Drosophila; D029721:Drosophila Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008565:Membrane Proteins; C494844:slo protein, Drosophila
keywords: Active zone; BK channel; Drosophila; Neuromuscular junction; PDZ domain; Scaffold protein