Why does fever trigger febrile seizures? GABAA receptor gamma2 subunit mutations associated with idiopathic generalized epilepsies have temperature-dependent trafficking deficiencies

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Jing-Qiong KangRobert L Macdonald

Abstract

With a worldwide incidence as high as 6.7% of children, febrile seizures are one of the most common reasons for seeking pediatric care, but the mechanisms underlying generation of febrile seizures are poorly understood. Febrile seizures have been suspected to have a genetic basis, and recently, mutations in GABAA receptor and sodium channel genes have been identified that are associated with febrile seizures and generalized seizures with febrile seizures plus pedigrees. Pentameric GABAA receptors mediate the majority of fast synaptic inhibition in the brain and are composed of combinations of alpha(1-6), beta(1-3), and gamma(1-3) subunits. In alphabetagamma2 GABAA receptors, the gamma2 subunit is critical for receptor trafficking, clustering, and synaptic maintenance, and mutations in the gamma2 subunit have been monogenically associated with autosomal dominant transmission of febrile seizures. Here, we report that whereas trafficking of wild-type alpha1beta2gamma2 receptors was slightly temperature dependent, trafficking of mutant alpha1beta2gamma2 receptors containing gamma2 subunit mutations [gamma2(R43Q), gamma2(K289M), and gamma2(Q351X)] associated with febrile seizures was highly temperature dependent. In contrast, traffi...Continue Reading

Citations

Jul 13, 2013·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Efterpi PavlidouChristos Panteliadis
Mar 31, 2010·Pflügers Archiv : European journal of physiology·Aristea S Galanopoulou
Feb 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·John C OakleyWilliam A Catterall
Oct 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·I Lorena Arancibia-CárcamoStephen J Moss
Nov 28, 2013·The Journal of General Physiology·Linda VolkersMartin B Rook
Jul 7, 2007·Cerebral Cortex·Marco FediDavid C Reutens
Sep 2, 2011·The Neurologist·Souhel NajjarOrrin Devinsky
Sep 19, 2007·Pediatric Emergency Care·Dante Pappano, Matthew Osborne
Apr 18, 2007·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·A O RossettiC Staedler
Sep 14, 2012·Epilepsia·J Helen Cross
Jan 30, 2007·Epilepsy Currents·Richard W Olsen
May 20, 2008·Epilepsy Currents·Carl E Stafstrom
Apr 28, 2009·Epilepsy Currents·Robert L Macdonald, Jing-Qiong Kang
Mar 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jing-Qiong KangRobert L Macdonald
Mar 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jing-Qiong KangRobert L Macdonald
Apr 8, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andrew J BoileauCynthia Czajkowski
Aug 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Martin J GallagherRobert L Macdonald
Mar 8, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Katelin P PattersonShlomo Shinnar
Oct 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Heneu O TanSteven Petrou
Jun 19, 2009·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Asuri N Prasad, Shashi S Seshia
Sep 23, 2008·Pediatric Neurology·Ozlem GirayDerya Erçal
Jul 4, 2007·Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners·Alexander K C Leung, W Lane M Robson
Aug 15, 2014·The Journal of Membrane Biology·Dhiraj KumarPravir Kumar
Sep 3, 2009·Neuroscience·M Siniatchkin, M Koepp
Jan 22, 2008·Molecular and Cellular Neurosciences·Karen A BollanChristopher N Connolly
Oct 28, 2008·Progress in Neurobiology·Christopher A ReidSteven Petrou
Feb 24, 2009·Brain & Development·Céline M DubéTallie Z Baram
Jul 11, 2006·Trends in Molecular Medicine·Samuel F Berkovic, Steven Petrou
Jan 9, 2013·Arquivos de neuro-psiquiatria·Sofia RochaÁlvaro Machado
May 16, 2017·Epilepsy Research·Timothy A WarnerJing-Qiong Kang
Jun 26, 2007·Brain & Development·Efterpi PavlidouChristos P Panteliadis
Apr 12, 2013·Journal of Child Neurology·Anup D Patel, Jorge Vidaurre
Apr 18, 2018·Expert Reviews in Molecular Medicine·Hao DengZhi Song
Sep 11, 2009·Annals of Neurology·Evan A ThomasSteven Petrou
May 1, 2008·Molecular Membrane Biology·C N Connolly
Jul 1, 2011·The European Journal of Neuroscience·Pamela Lachance-TouchettePatrick Cossette

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.