A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation

Martin Puskarjov, Patricia Seja, Sarah E Heron, Tristiana C Williams, Faraz Ahmad, Xenia Iona, Karen L Oliver, Bronwyn E Grinton, Laszlo Vutskits, Ingrid E Scheffer, Steven Petrou, Peter Blaesse, Leanne M Dibbens, Samuel F Berkovic, Kai Kaila

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

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.

Originalspråkengelska
TidskriftEMBO Reports
Volym15
Utgåva6
Sidor (från-till)723-729
Antal sidor7
ISSN1469-221X
DOI
StatusPublicerad - 25 mar 2014
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi

Citera det här

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. / A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. I: EMBO Reports. 2014 ; Vol. 15, Nr. 6. s. 723-729.
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title = "A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation",
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.",
keywords = "1182 Biochemistry, cell and molecular biology",
author = "Martin Puskarjov and Patricia Seja and Heron, {Sarah E} and Williams, {Tristiana C} and Faraz Ahmad and Xenia Iona and Oliver, {Karen L} and Grinton, {Bronwyn E} and Laszlo Vutskits and Scheffer, {Ingrid E} and Steven Petrou and Peter Blaesse and Dibbens, {Leanne M} and Berkovic, {Samuel F} and Kai Kaila",
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Puskarjov, M, Seja, P, Heron, SE, Williams, TC, Ahmad, F, Iona, X, Oliver, KL, Grinton, BE, Vutskits, L, Scheffer, IE, Petrou, S, Blaesse, P, Dibbens, LM, Berkovic, SF & Kaila, K 2014, 'A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation', EMBO Reports, vol. 15, nr. 6, s. 723-729. https://doi.org/10.1002/embr.201438749

A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation. / 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.

I: EMBO Reports, Vol. 15, Nr. 6, 25.03.2014, s. 723-729.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - A variant of KCC2 from patients with febrile seizures impairs neuronal Cl- extrusion and dendritic spine formation

AU - Puskarjov, Martin

AU - Seja, Patricia

AU - Heron, Sarah E

AU - Williams, Tristiana C

AU - Ahmad, Faraz

AU - Iona, Xenia

AU - Oliver, Karen L

AU - Grinton, Bronwyn E

AU - Vutskits, Laszlo

AU - Scheffer, Ingrid E

AU - Petrou, Steven

AU - Blaesse, Peter

AU - Dibbens, Leanne M

AU - Berkovic, Samuel F

AU - Kaila, Kai

PY - 2014/3/25

Y1 - 2014/3/25

N2 - 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.

AB - 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.

KW - 1182 Biochemistry, cell and molecular biology

U2 - 10.1002/embr.201438749

DO - 10.1002/embr.201438749

M3 - Article

VL - 15

SP - 723

EP - 729

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 6

ER -