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Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons
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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In the citing paper
“they regulate the functional state and number of AMPA-Rs – by phosphorylation or by changing the trafficking of AMPA-R subunits to and from the cell membrane (Passafaro et al., 2001; Montgomery and Madison, 2004; Bagal et al., 2005).”
From The Computational Anatomy of Psychosis (2013) · cites this paper as Passafaro et al., 2001
In the citing paper
“Lateral diffusion of receptors through the plasma membrane and activity-triggered exocytosis of receptors from internal endosomal compartments have become generally accepted regulation mechanisms for synaptic plasticity, although their respective contributions have remained unresolved”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Passafaro et al., 2001
In the citing paper
“although their respective contributions have remained unresolved (Passafaro et al., 2001; Borgdorff and Choquet, 2002; Adesnik et al., 2005; Ashby et al., 2006; Park et al., 2006; Ehlers et al., 2007; Heine et al., 2008; Newpher and Ehlers, 2008; Yang et al., 2008; Kennedy et al., 2010; Opazo and Choquet, 2011; Czöndör et al., 2012; Czöndör and Thoumine, 2013).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Passafaro et al., 2001
In the citing paper
“Whereas previously the cytoplasmic tails of GluA receptors have been shown to differentially regulate receptor diffusion and trapping at synapses (Passafaro et al., 2001)”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Passafaro et al., 2001
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Metadata
- Authors
- Passafaro, M., Piëch, V., & Sheng, M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Sheng, Morgan
- Venue
- Nature Neuroscience
- Published
- 2001-08-20
- Volume
- 4
- Issue
- 9
- Pages
- 917-926
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- 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
- 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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