scholarly journals Gating the channel pore of ionotropic glutamate receptors with bacterial substrate binding proteins

2021 ◽  
Author(s):  
Max Bernhard ◽  
Bodo Laube
Keyword(s):  
Glutamate Receptors ◽  
Binding Proteins ◽  
Disulfide Bridge ◽  
Ionotropic Glutamate Receptors ◽  
Functional Coupling ◽  
Channel Pore ◽  
Channel Current ◽  
Binding Domains ◽  
Bacterial Binding ◽  
Excitatory Neurotransmission

AbstractTetrameric ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission in the mammalian central nervous system and are involved in learning, memory formation, and pathological processes. Based on structural and sequence similarities of the ligand-binding and channel domains of iGluR subunits to bacterial binding proteins and potassium channels, iGluRs are thought to have originally arisen from their fusion. Here we report the functional coupling of the bacterial ectoine binding protein EhuB to the channel pore-forming transmembrane domains of the bacterial GluR0 receptor by stabilization of dimeric binding domains. Insertion of a disulfide bridge in the dimer interface abolished desensitization of the channel current analogous to mammalian iGluRs. These results demonstrate the functional compatibility of bacterial binding proteins to the gate of the channel pore of an iGluR. Moreover, our results highlight the modular structure and crucial role of binding domain dimerization in the functional evolution of iGluRs.

scholarly journals Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

2022 ◽  
Vol 14 ◽  
Author(s):  
Shuang Chen ◽  
Da Xu ◽  
Liu Fan ◽  
Zhi Fang ◽  
Xiufeng Wang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Glutamate Receptors ◽  
Neurological Disorders ◽  
Nerve Conduction ◽  
Ionotropic Glutamate Receptors ◽  
Future Studies ◽  
Excitatory Neurotransmission ◽  
The Relationship ◽  
Neuron Injury

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.

Neurosteroid binding to the amino terminal and glutamate binding domains of ionotropic glutamate receptors

Steroids ◽  
2012 ◽  
Vol 77 (7) ◽  
pp. 774-779 ◽  
Author(s):  
Krasnodara Cameron ◽  
Emily Bartle ◽  
Ryan Roark ◽  
David Fanelli ◽  
Melissa Pham ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Amino Terminal ◽  
Binding Domains ◽  
Glutamate Binding

scholarly journals NMDA and AMPA Receptors: Development and Status Epilepticus

2013 ◽  
pp. S21-S38 ◽  
Author(s):  
E. SZCZUROWSKA ◽  
P. MAREŠ
Keyword(s):  
Status Epilepticus ◽  
Glutamate Receptors ◽  
Ampa Receptors ◽  
Ionotropic Glutamate Receptors ◽  
Cognitive Disability ◽  
Excitatory Neurotransmitter ◽  
Functional Changes ◽  
Excitatory Neurotransmission ◽  
Intensive Investigation ◽  
High Level

Glutamate is the main excitatory neurotransmitter in the brain and ionotropic glutamate receptors mediate the majority of excitatory neurotransmission (Dingeldine et al. 1999). The high level of glutamatergic excitation allows the neonatal brain (the 2nd postnatal week in rat) to develop quickly but it also makes it highly prone to age-specific seizures that can cause lifelong neurological and cognitive disability (Haut et al. 2004). There are three types of ionotropic glutamate receptors (ligand-gated ion channels) named according to their prototypic agonists: N-methyl-D-aspartate (NMDA), 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) and kainate (KA). During early stages of postnatal development glutamate receptors of NMDA and AMPA type undergo intensive functional changes owing to modifications in their subunit composition (Carter et al. 1988, Watanabe et al. 1992, Monyer et al. 1994, Wenzel et al. 1997, Sun et al. 1998, Lilliu et al. 2001, Kumar et al. 2002, Matsuda et al. 2002, Wee et al. 2008, Henson et al. 2010, Pachernegg et al. 2012, Paoletti et al. 2013). Participation and role of these receptors in mechanisms of seizures and epilepsy became one of the main targets of intensive investigation (De Sarro et al. 2005, Di Maio et al. 2012, Rektor 2013). LiCl/Pilocarpine (LiCl/Pilo) induced status epilepticus is a model of severe seizures resulting in development temporal lobe epilepsy (TLE). This review will consider developmental changes and contribution of NMDA and AMPA receptors in LiCl/Pilo model of status epilepticus in immature rats.

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...

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