Impact of Synaptic Localization and Subunit Composition of Ionotropic Glutamate Receptors on Synaptic Function: Modeling and Simulation Studies

2017 ◽  
Vol 14 (4) ◽  
pp. 892-904 ◽  
Author(s):  
Anne Florence Keller ◽  
Nicolas Ambert ◽  
Arnaud Legendre ◽  
Mathieu Bedez ◽  
Jean-Marie Bouteiller ◽  
...  
Keyword(s):  
Modeling And Simulation ◽  
Glutamate Receptors ◽  
Synaptic Function ◽  
Subunit Composition ◽  
Ionotropic Glutamate Receptors ◽  
Simulation Studies ◽  
Synaptic Localization

scholarly journals The Reactive Plasticity of Hippocampal Ionotropic Glutamate Receptors in Animal Epilepsies

2019 ◽  
Vol 20 (5) ◽  
pp. 1030
Author(s):  
András Mihály
Keyword(s):  
Glutamate Receptors ◽  
Hippocampal Formation ◽  
Epileptic Seizures ◽  
Subunit Composition ◽  
Ionotropic Glutamate Receptors ◽  
Synaptic Membranes ◽  
Scaffolding Proteins ◽  
Interacting Proteins ◽  
Post Translational Modifications ◽  
Functional Receptor

Ionotropic glutamate receptors (iGluRs) mediate the synaptic and metabolic actions of glutamate. These iGluRs are classified within the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type, kainate-type, and N-methyl-d-aspartate (NMDA)-type functional receptor families. The iGluR assemblies are regulated by transcription, alternative splicing, and cytoplasmic post-translational modifications. The iGluR subunit proteins are transported from the endoplasmic reticulum, inserted into the synaptic membranes, and anchored at their action site by different scaffolding and interacting proteins. The functional properties of iGluRs depend on their subunit composition, the amino acid sequence of the protein domains, and the scaffolding proteins in the synaptic membranes. The iGluRs are removed from the membranes by enzymatic action and endocytosis. Hippocampal iGluRs are rearranged through the upregulation and downregulation of the subunits following deafferentation and epileptic seizures. The rearrangement of iGluRs and the alteration of their subunit composition transform neurons into “pathological” cells, determining the further plasticity or pathology of the hippocampal formation. In the present review, we summarize the expression of AMPA, kainate, and NMDA receptor subunits following deafferentation, repeated mild seizures, and status epilepticus. We compare our results to literature descriptions, and draw conclusions as to the reactive plasticity of iGluRs in the hippocampus.

scholarly journals AMPA receptor auxiliary subunits emerged during early vertebrate evolution by neo/subfunctionalization of unrelated proteins

Open Biology ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 200234
Author(s):  
David Ramos-Vicente ◽  
Àlex Bayés
Keyword(s):  
Glutamate Receptors ◽  
Animal Species ◽  
Vertebrate Evolution ◽  
Ionotropic Glutamate Receptors ◽  
Protein Families ◽  
Animal Evolution ◽  
Synaptic Localization ◽  
Auxiliary Subunits ◽  
Electrophysiological Properties ◽  
Consequent Increase

In mammalian synapses, the function of ionotropic glutamate receptors is critically modulated by auxiliary subunits. Most of these specifically regulate the synaptic localization and electrophysiological properties of AMPA-type glutamate receptors (AMPARs). Here, we comprehensively investigated the animal evolution of the protein families that contain AMPAR auxiliary subunits (ARASs). We observed that, on average, vertebrates have four times more ARASs than other animal species. We also demonstrated that ARASs belong to four unrelated protein families: CACNG-GSG1, cornichon, shisa and Dispanin C. Our study demonstrates that, despite the ancient origin of these four protein families, the majority of ARASs emerged during vertebrate evolution by independent but convergent processes of neo/subfunctionalization that resulted in the multiple ARASs found in present vertebrate genomes. Importantly, although AMPARs appeared and diversified in the ancestor of bilateral animals, the ARAS expansion did not occur until much later, in early vertebrate evolution. We propose that the surge in ARASs and consequent increase in AMPAR functionalities, contributed to the increased complexity of vertebrate brains and cognitive functions.

Glycine agonism in ionotropic glutamate receptors

2021 ◽  
pp. 108631
Author(s):  
David Stroebel ◽  
Laetitia Mony ◽  
Pierre Paoletti
Keyword(s):  
Glutamate Receptors ◽  
Ionotropic Glutamate Receptors

Preparation of domoic acid analogues using a bioconversion system, and their toxicity in mice

2021 ◽  
Author(s):  
Yukari Maeno ◽  
Yuichi Kotaki ◽  
Ryuta Terada ◽  
Masafumi Hidaka ◽  
Yuko Cho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chemical Synthesis ◽  
Glutamate Receptors ◽  
Domoic Acid ◽  
Ionotropic Glutamate Receptors ◽  
The Central Nervous System ◽  
Potent Agonist

Domoic acid (1, DA), a member of the natural kainoid family, is a potent agonist of ionotropic glutamate receptors in the central nervous system. The chemical synthesis of DA and...

scholarly journals NMDA and AMPA Receptor Autoantibodies in Brain Disorders: From Molecular Mechanisms to Clinical Features

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 77
Author(s):  
Fabrizio Gardoni ◽  
Jennifer Stanic ◽  
Diego Scheggia ◽  
Alberto Benussi ◽  
Barbara Borroni ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Ampa Receptor ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
In Vivo Studies ◽  
Ionotropic Glutamate Receptors ◽  
Brain Disorders ◽  
Functional Impairments ◽  
Different Types

The role of autoimmunity in central nervous system (CNS) disorders is rapidly expanding. In the last twenty years, different types of autoantibodies targeting subunits of ionotropic glutamate receptors have been found in a variety of patients affected by brain disorders. Several of these antibodies are directed against NMDA receptors (NMDAR), mostly in autoimmune encephalitis, whereas a growing field of research has identified antibodies against AMPA receptor (AMPAR) subunits in patients with different types of epilepsy or frontotemporal dementia. Several in vitro and in vivo studies performed in the last decade have dramatically improved our understanding of the molecular and functional effects induced by both NMDAR and AMPAR autoantibodies at the excitatory glutamatergic synapse and, consequently, their possible role in the onset of clinical symptoms. In particular, the method by which autoantibodies can modulate the localization at synapses of specific target subunits leading to functional impairments and behavioral alterations has been well addressed in animal studies. Overall, these preclinical studies have opened new avenues for the development of novel pharmacological treatments specifically targeting the synaptic activation of ionotropic glutamate receptors.

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