Ligand recognition in glutamate receptors: insights from mutagenesis of the soluble α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-binding domain of glutamate receptor type D (GluR-D)

1997 ◽  
Vol 25 (3) ◽  
pp. 835-838 ◽  
Author(s):  
K. Keinänen ◽  
M. Arvola ◽  
A. Kuusinen ◽  
M. Johnson
Keyword(s):  
Glutamate Receptors ◽  
Propionic Acid ◽  
Glutamate Receptor ◽  
Binding Domain ◽  
Receptor Type ◽  
Ligand Recognition ◽  
Type D

scholarly journals KEL-8 Is a Substrate Receptor for CUL3-dependent Ubiquitin Ligase That Regulates Synaptic Glutamate Receptor Turnover

2006 ◽  
Vol 17 (3) ◽  
pp. 1250-1260 ◽  
Author(s):  
Henry Schaefer ◽  
Christopher Rongo
Keyword(s):  
Caenorhabditis Elegans ◽  
Glutamate Receptors ◽  
Propionic Acid ◽  
Glutamate Receptor ◽  
Ubiquitin Ligase ◽  
Ubiquitin Ligases ◽  
Synaptic Proteins ◽  
Neuronal Protein ◽  
Cullin 3 ◽  
Receptor Turnover

The regulated localization of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (AMPARs) to synapses is an important component of synaptic signaling and plasticity. Regulated ubiquitination and endocytosis determine the synaptic levels of AMPARs, but it is unclear which factors conduct these processes. To identify genes that regulate AMPAR synaptic abundance, we screened for mutants that accumulate high synaptic levels of the AMPAR subunit GLR-1 in Caenorhabditis elegans. GLR-1 is localized to postsynaptic clusters, and mutants for the BTB-Kelch protein KEL-8 have increased GLR-1 levels at clusters, whereas the levels and localization of other synaptic proteins seem normal. KEL-8 is a neuronal protein and is localized to sites adjacent to GLR-1 postsynaptic clusters along the ventral cord neurites. KEL-8 is required for the ubiquitin-mediated turnover of GLR-1 subunits, and kel-8 mutants show an increased frequency of spontaneous reversals in locomotion, suggesting increased levels of GLR-1 are present at synapses. KEL-8 binds to CUL-3, a Cullin 3 ubiquitin ligase subunit that we also find mediates GLR-1 turnover. Our findings indicate that KEL-8 is a substrate receptor for Cullin 3 ubiquitin ligases that is required for the proteolysis of GLR-1 receptors and suggest a novel postmitotic role in neurons for Kelch/CUL3 ubiquitin ligases.

LIGAND RECOGNITION IN GLUTAMATE RECEPTORS: INSIGHTS FROM MUTAGENESIS OF THE SOLUBLE AMPA-BINDING DOMAIN OF GLUR-D

1997 ◽  
Vol 25 (3) ◽  
pp. 535S-535S
Author(s):  
K. Keinänen ◽  
M. Arvola ◽  
A. Kuusinen ◽  
M. Johnson
Keyword(s):  
Glutamate Receptors ◽  
Binding Domain ◽  
Ligand Recognition

scholarly journals Ligand-directed two-step labeling to quantify neuronal glutamate receptor trafficking

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kento Ojima ◽  
Kazuki Shiraiwa ◽  
Kyohei Soga ◽  
Tomohiro Doura ◽  
Mikiko Takato ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Receptor Trafficking ◽  
Protein Labeling ◽  
Selective Labeling ◽  
Receptor Localization ◽  
Glutamate Receptor Trafficking ◽  
Versatile Tool ◽  
The Central Nervous System ◽  
Long Lifetime

AbstractThe regulation of glutamate receptor localization is critical for development and synaptic plasticity in the central nervous system. Conventional biochemical and molecular biological approaches have been widely used to analyze glutamate receptor trafficking, especially for α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-type glutamate receptors (AMPARs). However, conflicting findings have been reported because of a lack of useful tools for analyzing endogenous AMPARs. Here, we develop a method for the rapid and selective labeling of AMPARs with chemical probes, by combining affinity-based protein labeling and bioorthogonal click chemistry under physiological temperature in culture medium. This method allows us to quantify AMPAR distribution and trafficking, which reveals some unique features of AMPARs, such as a long lifetime and a rapid recycling in neurons. This method is also successfully expanded to selectively label N-methyl-D-aspartate-type glutamate receptors. Thus, bioorthogonal two-step labeling may be a versatile tool for investigating the physiological and pathophysiological roles of glutamate receptors in neurons.

A Folded Excited State of Ligand-Free Nuclear Coactivator Binding Domain (NCBD) Underlies Plasticity in Ligand Recognition

Biochemistry ◽  
2013 ◽  
Vol 52 (10) ◽  
pp. 1686-1693 ◽  
Author(s):  
Magnus Kjaergaard ◽  
Lisbeth Andersen ◽  
Lau Dalby Nielsen ◽  
Kaare Teilum
Keyword(s):  
Excited State ◽  
Binding Domain ◽  
Ligand Recognition ◽  
Ligand Free

scholarly journals Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface

Neuron ◽  
2012 ◽  
Vol 76 (3) ◽  
pp. 565-578 ◽  
Author(s):  
Julien Veran ◽  
Janesh Kumar ◽  
Paulo S. Pinheiro ◽  
Axel Athané ◽  
Mark L. Mayer ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Glutamate Receptor ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Receptor Function ◽  
Dimer Interface

Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in ‘pattern II multiple sclerosis’ and brain biopsy findings in a MOG-IgG-positive case

2016 ◽  
Vol 22 (12) ◽  
pp. 1541-1549 ◽  
Author(s):  
Sven Jarius ◽  
Imke Metz ◽  
Fatima Barbara König ◽  
Klemens Ruprecht ◽  
Markus Reindl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Brain Biopsy ◽  
Acid Decarboxylase ◽  
Gamma Aminobutyric Acid ◽  
Serum Samples ◽  
Metabotropic Glutamate ◽  
Histopathological Studies

Background: Histopathological studies have revealed four different immunopathological patterns of lesion pathology in early multiple sclerosis (MS). Pattern II MS is characterised by immunoglobulin and complement deposition in addition to T-cell and macrophage infiltration and is more likely to respond to plasma exchange therapy, suggesting a contribution of autoantibodies. Objective: To assess the frequency of anti-myelin oligodendrocyte glycoprotein (MOG), anti-M1-aquaporin-4 (AQP4), anti-M23-AQP4, anti-N-methyl-d-aspartate-type glutamate receptors (NMDAR) and 25 other anti-neural antibodies in pattern II MS. Methods: Thirty-nine serum samples from patients with MS who had undergone brain biopsy ( n = 24; including 13 from patients with pattern II MS) and from histopathologically non-classified MS patients ( n = 15) were tested for anti-MOG, anti-M1-AQP4, anti-M23-AQP4, anti-NMDAR, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-type glutamate receptors (AMPAR), anti-gamma-aminobutyric acid receptors (GABABR), anti-leucine-rich, glioma-activated protein 1 (LGI1), anti-contactin-associated protein 2 (CASPR2), anti-dipeptidyl-peptidase-like protein-6 (DPPX), anti-Tr/Delta/notch-like epidermal growth factor–related receptor (DNER), anti-Hu, anti-Yo, anti-Ri, anti-Ma1/Ma2, anti-CV2/collapsin response mediator protein 5 (CRMP5), anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Ca/RhoGTPase-activating protein 26 (ARHGAP26), anti-Sj/inositol-1,4,5-trisphosphate receptor 1 (ITPR1), anti-Homer3, anti-carbonic anhydrase–related protein (CARPVIII), anti-protein kinase gamma (PKCgamma), anti-glutamate receptor delta 2 (GluRdelta2), anti-metabotropic glutamate receptor 1 (mGluR1) and anti-mGluR5, as well as for anti-glial nuclei antibodies (AGNA) and Purkinje cell antibody 2 (PCA2). Results: Antibodies to MOG belonging to the complement-activating immunoglobulin G1 (IgG1) subclass were detected in a patient with pattern II MS. Detailed brain biopsy findings are shown. Conclusion: This is the largest study on established anti-neural antibodies performed in MS so far. MOG-IgG may play a role in a small percentage of patients diagnosed with pattern II MS.

Sign in / Sign up

Export Citation Format

Share Document