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

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 cellul...

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Veröffentlicht in:Molecular neurobiology 2011-08, Vol.44 (1), p.111-121
Hauptverfasser: Azizieh, Régis, Orduz, David, Van Bogaert, Patrick, Bouschet, Tristan, Rodriguez, Wendy, Schiffmann, Serge N., Pirson, Isabelle, Abramowicz, Marc J.
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container_end_page 121
container_issue 1
container_start_page 111
container_title Molecular neurobiology
container_volume 44
creator Azizieh, Régis
Orduz, David
Van Bogaert, Patrick
Bouschet, Tristan
Rodriguez, Wendy
Schiffmann, Serge N.
Pirson, Isabelle
Abramowicz, Marc J.
description 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.
doi_str_mv 10.1007/s12035-011-8194-0
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source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Action Potentials - physiology
Animals
Antibody Specificity
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell membranes
Cells, Cultured
Cercopithecus aethiops
COS Cells
Cullin
Cullin Proteins - metabolism
Epilepsy
Excitability
Gene Expression Regulation
Genes
Hippocampus
Hippocampus - metabolism
Hippocampus - pathology
Homology
Humans
Immunoprecipitation
Ion Channel Gating - genetics
Membrane potential
Mice
Myoclonic Epilepsies, Progressive - genetics
Neurobiology
Neurology
Neurons
Neurons - metabolism
Neurons - pathology
Neurosciences
Nonsense mutation
Olfactory Bulb - metabolism
Olfactory Bulb - pathology
Phenotypes
Potassium
Potassium Channels - genetics
Potassium Channels - metabolism
Potassium conductance
Poxvirus
Protein Binding
Protein Multimerization
Protein Transport
Purkinje cells
Purkinje Cells - metabolism
Purkinje Cells - pathology
RNA, Messenger - genetics
RNA, Messenger - metabolism
Zinc finger proteins
title Progressive Myoclonic Epilepsy-Associated Gene KCTD7 is a Regulator of Potassium Conductance in Neurons
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