title: Krüppel mediates the selective rebalancing of ion channel expression.
abstract: Ion channel gene expression can vary substantially among neurons of a given type, even though neuron-type-specific firing properties remain stable and reproducible. The mechanisms that modulate ion channel gene expression and stabilize neural firing properties are unknown. In Drosophila, we demonstrate that loss of the Shal potassium channel induces the compensatory rebalancing of ion channel expression including, but not limited to, the enhanced expression and function of Shaker and slowpoke. Using genomic and network modeling approaches combined with genetic and electrophysiological assays, we demonstrate that the transcription factor Krüppel is necessary for the homeostatic modulation of Shaker and slowpoke expression. Remarkably, Krüppel induction is specific to the loss of Shal, not being observed in five other potassium channel mutants that cause enhanced neuronal excitability. Thus, homeostatic signaling systems responsible for rebalancing ion channel expression can be selectively induced after the loss or impairment of a specific ion channel.
authors.affiliation: Department of Biology, University of Washington, Seattle, WA 98195, USA. Electronic address: jzp2@uw.edu.
authors.forename: Jay Z
authors.initials: JZ
authors.lastname: Parrish
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA. Electronic address: charlie.kim@ucsf.edu.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Lamont
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Bergquist
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Derisi
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: graeme.davis@ucsf.edu.
authors.forename: Graeme W
authors.initials: GW
authors.lastname: Davis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology*; D007473:Ion Channels / Q000096:biosynthesis* / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D051672:Shal Potassium Channels / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D007473:Ion Channels; C497244:Kr protein, Drosophila; D051741:Kruppel-Like Transcription Factors; D051672:Shal Potassium Channels; C497024:Shal protein, Drosophila