Activation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations

In the central nervous system, the M-current plays a critical role in regulating subthreshold electrical excitability of neurons, determining their firing properties and responsiveness to synaptic input. The M-channel is mainly formed by subunits Kv7.2 and Kv7.3 that co-assemble to form a heterotetr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elva Martin-Batista, Rían W. Manville, Belinda Rivero-Pérez, David Bartolomé-Martín, Diego Alvarez de la Rosa, Geoffrey W. Abbott, Teresa Giraldez
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	serum and glucocorticoid-induced kinase Kv7 channels KCNQ epilepsy SGK1.1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/f97174501a0741d39ac4467b2b44bfa8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f97174501a0741d39ac4467b2b44bfa8
record_format	dspace
spelling	oai:doaj.org-article:f97174501a0741d39ac4467b2b44bfa82021-12-01T07:59:49ZActivation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations1662-509910.3389/fnmol.2021.798261https://doaj.org/article/f97174501a0741d39ac4467b2b44bfa82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnmol.2021.798261/fullhttps://doaj.org/toc/1662-5099In the central nervous system, the M-current plays a critical role in regulating subthreshold electrical excitability of neurons, determining their firing properties and responsiveness to synaptic input. The M-channel is mainly formed by subunits Kv7.2 and Kv7.3 that co-assemble to form a heterotetrametric channel. Mutations in Kv7.2 and Kv7.3 are associated with hyperexcitability phenotypes including benign familial neonatal epilepsy (BFNE) and neonatal epileptic encephalopathy (NEE). SGK1.1, the neuronal isoform of the serum and glucocorticoids-regulated kinase 1 (SGK1), increases M-current density in neurons, leading to reduced excitability and protection against seizures. Herein, using two-electrode voltage clamp on Xenopus laevis oocytes, we demonstrate that SGK1.1 selectively activates heteromeric Kv7 subunit combinations underlying the M-current. Importantly, activated SGK1.1 increases M-channel activity in the presence of two different epilepsy mutations found in Kv7.2, R207W and A306T. In addition, proximity ligation assays in the N2a cell line allowed us to address the effect of these mutations on Kv7-SGK1.1-Nedd4 molecular associations, a proposed pathway underlying augmentation of M-channel activity by SGK1.1Elva Martin-BatistaRían W. ManvilleBelinda Rivero-PérezDavid Bartolomé-MartínDiego Alvarez de la RosaGeoffrey W. AbbottTeresa GiraldezFrontiers Media S.A.articleserum and glucocorticoid-induced kinaseKv7 channelsKCNQepilepsySGK1.1Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Molecular Neuroscience, Vol 14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	serum and glucocorticoid-induced kinase Kv7 channels KCNQ epilepsy SGK1.1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	serum and glucocorticoid-induced kinase Kv7 channels KCNQ epilepsy SGK1.1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Elva Martin-Batista Rían W. Manville Belinda Rivero-Pérez David Bartolomé-Martín Diego Alvarez de la Rosa Geoffrey W. Abbott Teresa Giraldez Activation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations
description	In the central nervous system, the M-current plays a critical role in regulating subthreshold electrical excitability of neurons, determining their firing properties and responsiveness to synaptic input. The M-channel is mainly formed by subunits Kv7.2 and Kv7.3 that co-assemble to form a heterotetrametric channel. Mutations in Kv7.2 and Kv7.3 are associated with hyperexcitability phenotypes including benign familial neonatal epilepsy (BFNE) and neonatal epileptic encephalopathy (NEE). SGK1.1, the neuronal isoform of the serum and glucocorticoids-regulated kinase 1 (SGK1), increases M-current density in neurons, leading to reduced excitability and protection against seizures. Herein, using two-electrode voltage clamp on Xenopus laevis oocytes, we demonstrate that SGK1.1 selectively activates heteromeric Kv7 subunit combinations underlying the M-current. Importantly, activated SGK1.1 increases M-channel activity in the presence of two different epilepsy mutations found in Kv7.2, R207W and A306T. In addition, proximity ligation assays in the N2a cell line allowed us to address the effect of these mutations on Kv7-SGK1.1-Nedd4 molecular associations, a proposed pathway underlying augmentation of M-channel activity by SGK1.1
format	article
author	Elva Martin-Batista Rían W. Manville Belinda Rivero-Pérez David Bartolomé-Martín Diego Alvarez de la Rosa Geoffrey W. Abbott Teresa Giraldez
author_facet	Elva Martin-Batista Rían W. Manville Belinda Rivero-Pérez David Bartolomé-Martín Diego Alvarez de la Rosa Geoffrey W. Abbott Teresa Giraldez
author_sort	Elva Martin-Batista
title	Activation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations
title_short	Activation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations
title_full	Activation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations
title_fullStr	Activation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations
title_full_unstemmed	Activation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations
title_sort	activation of sgk1.1 upregulates the m-current in the presence of epilepsy mutations
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f97174501a0741d39ac4467b2b44bfa8
work_keys_str_mv	AT elvamartinbatista activationofsgk11upregulatesthemcurrentinthepresenceofepilepsymutations AT rianwmanville activationofsgk11upregulatesthemcurrentinthepresenceofepilepsymutations AT belindariveroperez activationofsgk11upregulatesthemcurrentinthepresenceofepilepsymutations AT davidbartolomemartin activationofsgk11upregulatesthemcurrentinthepresenceofepilepsymutations AT diegoalvarezdelarosa activationofsgk11upregulatesthemcurrentinthepresenceofepilepsymutations AT geoffreywabbott activationofsgk11upregulatesthemcurrentinthepresenceofepilepsymutations AT teresagiraldez activationofsgk11upregulatesthemcurrentinthepresenceofepilepsymutations
_version_	1718405452932317184

Activation of SGK1.1 Upregulates the M-current in the Presence of Epilepsy Mutations

Ejemplares similares