Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12142
Title: A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation.
Authors: Puskarjov, Martin;Seja, Patricia;Heron, Sarah E;Williams, Tristiana C;Ahmad, Faraz;Iona, Xenia;Oliver, Karen L;Grinton, Bronwyn E;Vutskits, Laszlo;Scheffer, Ingrid E;Petrou, Steven;Blaesse, Peter;Dibbens, Leanne M;Berkovic, Samuel F;Kaila, Kai
Affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland Neuroscience Center, University of Helsinki, Helsinki, Finland.
Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
Department of Medicine, Epilepsy Research Center, The University of Melbourne Austin Health, Melbourne Vic., Australia.
Department of Paediatrics, Florey Institute, Royal Children's Hospital The University of Melbourne, Melbourne, Vic., Australia.
Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Geneva, Switzerland.
Department of Medicine, Epilepsy Research Center, The University of Melbourne Austin Health, Melbourne Vic., Australia Department of Paediatrics, Florey Institute, Royal Children's Hospital The University of Melbourne, Melbourne, Vic., Australia.
Florey Institute of Neuroscience and Mental Health and the Center for Neural Engineering, The University of Melbourne, Parkville, Vic., Australia.
Department of Biosciences, University of Helsinki, Helsinki, Finland Institute of Physiology I, Westfälische Wilhelms-University Münster, Münster, Germany.
Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Sansom Institute for Health Research, University of South Australia, Adelaide SA, Australia.
Department of Biosciences, University of Helsinki, Helsinki, Finland Neuroscience Center, University of Helsinki, Helsinki, Finland Kai.Kaila@Helsinki.fi.
Issue Date: 24-Mar-2014
Citation: Embo Reports 2014; 15(6): 723-9
Abstract: Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in an Australian family with febrile seizures. We show that KCC2-R952H reduces neuronal Cl(-) extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2-R952H which likely contributes to the functional deficits. Our data suggest that KCC2-R952H is a bona fide susceptibility variant for febrile seizures.
Internal ID Number: 24668262
URI: http://ahro.austin.org.au/austinjspui/handle/1/12142
DOI: 10.1002/embr.201438749
URL: http://www.ncbi.nlm.nih.gov/pubmed/24668262
Type: Journal Article
Subjects: KCC2
dendritic spines
febrile seizures
genic intolerance
mutation
Amino Acid Sequence
Animals
Australia
Blotting, Western
Chlorides.metabolism
Dendritic Spines.genetics.pathology
Genetic Predisposition to Disease.genetics
Humans
Mice
Mice, Inbred ICR
Microscopy, Fluorescence
Models, Molecular
Molecular Sequence Data
Mutation, Missense.genetics
Neurons.metabolism
Pedigree
Protein Conformation
Rats
Rats, Wistar
Seizures, Febrile.genetics
Statistics, Nonparametric
Symporters.genetics.metabolism
Appears in Collections:Journal articles

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