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Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons

Passafaro, Maria, Piëch, Valentin, Sheng, Morgan·2001·Nature Neuroscience

DOI 10.1038/nn0901-917

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Abstract

Using a thrombin cleavage assay in cultured hippocampal neurons, we studied the kinetics, regulation and site of AMPA receptor surface delivery. Surface insertion of the GluR1 subunit occurs slowly in basal conditions and is stimulated by NMDA receptor activation and insulin, whereas GluR2 exocytosis is constitutively rapid. Although both subunits ultimately concentrate in synapses, GluR1 and GluR2 show different spatial patterns of surface accumulation, consistent with GluR1 being inserted initially at extrasynaptic sites and GluR2 being inserted more directly at synapses. The spatiotemporal pattern of surface accumulation is determined by the cytoplasmic tails of GluR subunits, and in heteromeric receptors, GluR1 acts dominantly over GluR2. We propose that GluR1 controls the exocytosis and GluR2/3, the recycling and endocytosis of AMPA receptors.

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Authors: Passafaro, M., Piëch, V., & Sheng, M.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Sheng, Morgan
ORCID: Passafaro, Maria
Sheng, Morgan
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2001-08-20
Volume: 4
Issue: 9
Pages: 917-926
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn0901-917
OpenAlex: W1993049854
Cited by: 655
References: 43
Citations by year: 2026: 3 · 2025: 6 · 2024: 10 · 2023: 4 · 2022: 13 · 2021: 14 · 2020: 18 · 2019: 14 · 2018: 17 · 2017: 15 · 2016: 22 · 2015: 22 · 2014: 21 · 2013: 28 · 2012: 24
FWCI: 16.82
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Neurological Disorders and Stroke (NS 35050, R01NS035050)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords: AMPA receptors, GluR1, GluR2, GluR3, hippocampal neurons, NMDA receptor activation, insulin, extrasynaptic receptors, synaptic receptors, cytoplasmic tail, heteromeric receptors, receptor recycling, endocytosis
MeSH terms: Amino Acid Sequence, Animals, Cell Membrane, Cells, Cultured, Exocytosis, Hippocampus, Neurons, Time Factors, Tissue Distribution, Receptors, AMPA, Protein Isoforms, Rats

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Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons

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