2015
DOI: 10.1038/cr.2015.75
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Activity-induced synaptic delivery of the GluN2A-containing NMDA receptor is dependent on endoplasmic reticulum chaperone Bip and involved in fear memory

Abstract: 2+-dependent signaling and synaptic plasticity. Previous studies have suggested that the synaptic trafficking of NMDAR subtypes is differentially regulated, but the precise molecular mechanism is not yet clear. In this study, we demonstrated that Bip, an endoplasmic reticulum (ER) chaperone, selectively interacted with GluN2A and mediated the neuronal activity-induced assembly and synaptic incorporation of the GluN2A-containing NMDAR from dendritic ER. Furthermore, the GluN2A-specific synaptic trafficking was … Show more

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Cited by 33 publications
(48 citation statements)
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“…To reinforce this conclusion, we investigated colocalization between Shp2 and PSD95 in dendrites with and without cLTP stimuli using a standard protocol (17,18) that selectively activates synaptic NMDA receptors. Statistical analysis of the colocalization illustrated that the proportion of Shp2 clusters (without cLTP treatment, 0.69 Ϯ 0.0056, n ϭ 15 neurons; cLTP treatment, 0.73 Ϯ 0.0054, n ϭ 15 neurons; two-tailed Student's t test, p Ͻ 0.005) that were merged with PSD95 clusters was markedly increased in the cLTP group (Fig.…”
Section: Resultsmentioning
confidence: 99%
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“…To reinforce this conclusion, we investigated colocalization between Shp2 and PSD95 in dendrites with and without cLTP stimuli using a standard protocol (17,18) that selectively activates synaptic NMDA receptors. Statistical analysis of the colocalization illustrated that the proportion of Shp2 clusters (without cLTP treatment, 0.69 Ϯ 0.0056, n ϭ 15 neurons; cLTP treatment, 0.73 Ϯ 0.0054, n ϭ 15 neurons; two-tailed Student's t test, p Ͻ 0.005) that were merged with PSD95 clusters was markedly increased in the cLTP group (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Induction of Chemical LTP-The cLTP protocol was adopted from previous publications (17,18). Hippocampal neurons were rinsed twice in non-magnesium ECS (143 mM NaCl, 5 mM KCl, 3 mM CaCl 2 , 10 mM HEPES, 10 mM glucose, pH 7.4), and incubated in ECS ϩ (non-magnesium ECS containing 0.5 M tetrodotoxin, 1 M strychnine, 20 M bicuculline) for 20 min.…”
Section: Methodsmentioning
confidence: 99%
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“…Bip, a recently discovered ER chaperone protein, is involved in the selective delivery of GluN2A-containing NMDAR at the synapse from the dendritic ER [107].…”
Section: Other Proteinsmentioning
confidence: 99%
“…We made maximal efforts to minimize animal numbers and to reduce animal suffering. Hippocampal primary neuronal cultures were harvested from embryonic day 18 Sprague-Dawley rats or newborn (postnatal day 1-2) Shp2 flox/flox mice of either sex, as described previously (9,29). Hippocampal tissue was quickly dissected in ice-cold Hanks' balanced salt solution (HBSS) buffer and then digested in 0.5% trypsin for 15 min at 37°C.…”
Section: Hippocampal Neuron Culture and Transfectionmentioning
confidence: 99%