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Author

Chen Zhang

Bio: Chen Zhang is an academic researcher from Capital Medical University. The author has contributed to research in topics: AMPA receptor & Long-term potentiation. The author has an hindex of 1, co-authored 1 publications receiving 8 citations.

Papers
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Journal ArticleDOI
TL;DR: In this paper, the amino-terminal domain (ATD) of GluA1 is found to be essential for long-term potentiation (LTP) maintenance.
Abstract: Long-term potentiation (LTP) has long been considered as an important cellular mechanism for learning and memory. LTP expression involves NMDA receptor-dependent synaptic insertion of AMPA receptors (AMPARs). However, how AMPARs are recruited and anchored at the postsynaptic membrane during LTP remains largely unknown. In this study, using CRISPR/Cas9 to delete the endogenous AMPARs and replace them with the mutant forms in single neurons, we have found that the amino-terminal domain (ATD) of GluA1 is required for LTP maintenance. Moreover, we show that GluA1 ATD directly interacts with the cell adhesion molecule neuroplastin-65 (Np65). Neurons lacking Np65 exhibit severely impaired LTP maintenance, and Np65 deletion prevents GluA1 from rescuing LTP in AMPARs-deleted neurons. Thus, our study reveals an essential role for GluA1/Np65 binding in anchoring AMPARs at the postsynaptic membrane during LTP.

21 citations


Cited by
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Journal ArticleDOI
TL;DR: In this paper, an updated AMPAR trafficking and LTP model was proposed, which incorporates both extracellular as well as intracellular mechanisms, based on recent research reviewed in this special issue on AMPA receptors.

28 citations

Journal ArticleDOI
TL;DR: An overview of the catalogue of AMPAR interacting proteins and how they contribute to the complex biology of this central glutamate receptor can be found in this article, where an array of transmembrane proteins operate as auxiliary subunits that in addition to receptor trafficking and stabilization also substantially impact AMPAR gating and pharmacology.

11 citations

Journal ArticleDOI
TL;DR: In this article, a de novo pathogenic missense variant in GRIA3 (c.1979G>C; p. R660T) was identified in a 1-year-old female patient with severe epilepsy and global developmental delay.
Abstract: The X-linked GRIA3 gene encodes the GLUA3 subunit of AMPA-type glutamate receptors. Pathogenic variants in this gene were previously reported in neurodevelopmental diseases, mostly in male patients but rarely in females. Here we report a de novo pathogenic missense variant in GRIA3 (c.1979G>C; p. R660T) identified in a 1-year-old female patient with severe epilepsy and global developmental delay. When exogenously expressed in human embryonic kidney (HEK) cells, GLUA3_R660T showed slower desensitization and deactivation kinetics compared to wildtype (wt) GLUA3 receptors. Substantial non-desensitized currents were observed with the mutant but not for wt GLUA3 with prolonged exposure to glutamate. When co-expressed with GLUA2, the decay kinetics were similarly slowed in GLUA2/A3_R660T with non-desensitized steady state currents. In cultured cerebellar granule neurons, miniature excitatory postsynaptic currents (mEPSCs) were significantly slower in R660T transfected cells than those expressing wt GLUA3. When overexpressed in hippocampal CA1 neurons by in utero electroporation, the evoked EPSCs and mEPSCs were slower in neurons expressing R660T mutant compared to those expressing wt GLUA3. Therefore our study provides functional evidence that a gain of function (GoF) variant in GRIA3 may cause epileptic encephalopathy and global developmental delay in a female subject by enhancing synaptic transmission.

11 citations

Journal ArticleDOI
TL;DR: In this article, the authors compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses, and show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission.
Abstract: AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is therefore tightly controlled. Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but with limited coherence or comparison between reports, our understanding of this process is unclear. Here, combining synaptic recordings from mouse hippocampal slices and super-resolution imaging in dissociated cultures, we compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses. We show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission. Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density, where the NTD further tunes their positioning. This interplay between cytosolic (TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate synaptic transmission and plasticity.

11 citations

Journal ArticleDOI
TL;DR: In this paper , the authors showed that Np65-specific extracellular domain of Np55-PMCA complexes can be used to regulate the duration and amplitude of cytosolic Ca2+ transients in dendrites and spines of hippocampal neurons.

7 citations