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Progressive Myoclonic Epilepsy-Associated Gene KCTD7 is a Regulator of Potassium Conductance in Neurons

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Abstract

The potassium channel tetramerization domain-containing protein 7 (KCTD7) was named after the structural homology of its predicted N-terminal broad complex, tramtrack and bric à brac/poxvirus and zinc finger domain with the T1 domain of the Kv potassium channel, but its expression profile and cellular function are still largely unknown. We have recently reported a homozygous nonsense mutation of KCTD7 in patients with a novel form of autosomal recessive progressive myoclonic epilepsy. Here, we show that KCTD7 expression hyperpolarizes the cell membrane and reduces the excitability of transfected neurons in patch clamp experiments. We found the expression of KCTD7 in the hippocampal and Purkinje cells of the murine brain, an expression profile consistent with our patients’ phenotype. The effect on the plasma membrane resting potential is possibly mediated by Cullin-3, as we demonstrated direct molecular interaction of KCTD7 with Cullin-3 in co-immunoprecipitation assays. Our data link progressive myoclonic epilepsy to an inherited defect of the neuron plasma membrane’s resting potential in the brain.

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Acknowledgments

Regis Azizieh is a PhD student supported by the FRIA (Fonds pour la formation à la Recherche dans l’Industrie et dans l’Agriculture) and Van Buuren grants. Marc J. Abramowicz and Serge N. Schiffmann are supported by FRSM (Fonds de la Recherche scientifique médicale) grants of the Belgian FNRS (Fonds national de la Recherche Scientifique), Marc J. Abramowicz is supported by the Fonds Erasme and Serge N. Schiffmann by grant from the Queen Elisabeth Medical foundation (FMRE, Belgium). We thank Pierre Vanderhaeghen and Alban de Kerchove d’Exaerde for discussion and Sandra Strollo, Chantal Degraef, Patrick Massoma and Sandra Pietri for expert technical help.

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Authors and Affiliations

  1. Institute of Interdisciplinary Research (IRIBHM)-ULB, Brussels, Belgium

    Régis Azizieh, Tristan Bouschet, Wendy Rodriguez, Isabelle Pirson & Marc J. Abramowicz

  2. Department of Medical Genetics, Hôpital Erasme–ULB, Brussels, Belgium

    Marc J. Abramowicz

  3. Laboratory of Neurophysiology-ULB, Brussels, Belgium

    David Orduz & Serge N. Schiffmann

  4. Department of Pediatric Neurology, Hôpital Erasme–ULB, Brussels, Belgium

    Patrick Van Bogaert

  5. Institute of Interdisciplinary Research, IRIBHM, School of Medicine, Free University of Brussels (ULB), Campus Erasme, Building C, 808, Route de Lennik, 1070, Brussels, Belgium

    Isabelle Pirson

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  1. Régis Azizieh
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Correspondence to Régis Azizieh.

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Azizieh, R., Orduz, D., Van Bogaert, P. et al. Progressive Myoclonic Epilepsy-Associated Gene KCTD7 is a Regulator of Potassium Conductance in Neurons. Mol Neurobiol 44, 111–121 (2011). https://doi.org/10.1007/s12035-011-8194-0

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