Deficits in phosphorylation of GABA(A) receptors by intimately associated protein kinase C activity underlie compromised synaptic inhibition during status epilepticus

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Miho TerunumaStephen J Moss

Abstract

Status epilepticus (SE) is a progressive and often lethal human disorder characterized by continuous or rapidly repeating seizures. Of major significance in the pathology of SE are deficits in the functional expression of GABA(A) receptors (GABA(A)Rs), the major sites of fast synaptic inhibition in the brain. We demonstrate that SE selectively decreases the phosphorylation of GABA(A)Rs on serine residues 408/9 (S408/9) in the beta3 subunit by intimately associated protein kinase C isoforms. Dephosphorylation of S408/9 unmasks a basic patch-binding motif for the clathrin adaptor AP2, enhancing the endocytosis of selected GABA(A)R subtypes from the plasma membrane during SE. In agreement with this, enhancing S408/9 phosphorylation or selectively blocking the binding of the beta3 subunit to AP2 increased GABA(A)R cell surface expression levels and restored the efficacy of synaptic inhibition in SE. Thus, enhancing phosphorylation of GABA(A)Rs or selectively blocking their interaction with AP2 may provide novel therapeutic strategies to ameliorate SE.

References

Jan 1, 1987·Annual Review of Neuroscience·N M Nathanson
Apr 2, 1998·The New England Journal of Medicine·D H Lowenstein, B K Alldredge
May 5, 1999·Current Opinion in Neurology·B K Alldredge, D H Lowenstein
Aug 13, 2002·Current Topics in Medicinal Chemistry·W Sieghart, G Sperk
Jun 24, 2003·Neuron·Qinghua WangYu Tian Wang
Jul 4, 2003·Methods in Molecular Biology·Peter J Parker
Jan 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jasmina N JovanovicStephen J Moss
Jan 28, 2004·Annual Review of Pharmacology and Toxicology·Jürgen Wess
Jul 13, 2004·Pharmacology & Therapeutics·Bernhard Lüscher, Cheryl A Keller
Aug 13, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Miho TerunumaMasato Hirata
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Josef T KittlerStephen J Moss
Jan 28, 2005·The European Journal of Neuroscience·Carolien van RijnsoeverJean-Marc Fritschy
Mar 2, 2005·Nature Reviews. Neuroscience·Mark Farrant, Zoltan Nusser
Jun 10, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Howard P GoodkinJaideep Kapur
Aug 27, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David E NaylorClaude G Wasterlain
Sep 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Josef T KittlerStephen J Moss
Dec 27, 2005·Current Opinion in Pharmacology·Uwe Rudolph, Hanns Möhler
Mar 3, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Guojun ChenZhen Yan
Sep 2, 2006·The EMBO Journal·Yury BogdanovStephen J Moss
Oct 5, 2006·Cell·Volker Haucke

❮ Previous
Next ❯

Citations

Oct 22, 2013·Trends in Neurosciences·Kristopher T KahleStephen J Moss
Apr 3, 2008·Nature Reviews. Neuroscience·Tija C JacobRachel Jurd
Oct 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·I Lorena Arancibia-CárcamoStephen J Moss
Nov 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Verena TretterStephen J Moss
Nov 28, 2009·Epilepsia·Matthew C Walker
May 9, 2012·PloS One·Fumihiro NiwaKatsuhiko Mikoshiba
Oct 7, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sangwook JungNicholas P Poolos
Dec 12, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Claudia GonzalezRichard W Olsen
Mar 1, 2012·Epilepsy Currents·Nicholas P Poolos
Aug 20, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Neal H BarmackVadim Yakhnitsa
Sep 27, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mansi VithlaniStephen J Moss
Dec 15, 2010·Indian Journal of Pediatrics·Dinesh RajRakesh Lodha
Dec 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Thuy N VienStephen J Moss
Mar 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Liliya SilayevaStephen J Moss
Aug 24, 2010·Seminars in Pediatric Neurology·Karthik RajasekaranHoward P Goodkin
Mar 23, 2010·Neurobiology of Disease·Zakaria MtchedlishviliKevin M Kelly
Aug 22, 2008·Epilepsy Research·Michaelangelo G FuortesLisa R Merlin
Dec 19, 2012·Epilepsia·Nicholas P Poolos, Daniel Johnston
May 30, 2013·Molecular and Cellular Neurosciences·Suchitra JoshiJaideep Kapur
Aug 17, 2014·Neuropharmacology·Paul D WhissellBeverley A Orser
Apr 20, 2013·Epilepsy Research·Fei TianDaiquan Gao
Jun 30, 2010·Communicative & Integrative Biology·Rachel Jurd, Stephen J Moss
Jun 1, 2014·The International Journal of Biochemistry & Cell Biology·Sahil Talwar, Joseph W Lynch
Jan 10, 2012·Experimental Neurology·Nicola Maggio, Menahem Segal
Jul 6, 2010·Molecular and Cellular Neurosciences·Henry H C LeeStephen J Moss
Apr 27, 2017·Journal of Veterinary Emergency and Critical Care·Susan Blades Golubovic, John H Rossmeisl
Mar 25, 2018·Annals of Neurology·Suchitra JoshiHoward P Goodkin
Jun 3, 2008·Journal of Neurochemistry·Joaquin N LugoAnne E Anderson
Nov 28, 2017·Drugs in R&D·John Benfield, Alberto Musto

❮ 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.

Related Papers

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Howard P GoodkinJ Kapur
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
David E NaylorClaude G Wasterlain
Proceedings of the National Academy of Sciences of the United States of America
Josef T KittlerStephen J Moss
Proceedings of the National Academy of Sciences of the United States of America
Josef T KittlerStephen J Moss
Proceedings of the National Academy of Sciences of the United States of America
I Lorena Arancibia-CarcamoStephen J Moss
© 2021 Meta ULC. All rights reserved