Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane
Open accessAbstract
Intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic function. However, little is known about the specialized trafficking events occurring at the postsynaptic membrane. We have found that two components of the exocyst complex, Sec8 and Exo70, separately control synaptic targeting and insertion of AMPA-type glutamate receptors. Sec8 controls the directional movement of receptors towards synapses through PDZ-dependent interactions. In contrast, Exo70 mediates receptor insertion at the postsynaptic membrane, but it does not participate in receptor targeting. Thus, interference with Exo70 function accumulates AMPA receptors inside the spine, forming a complex physically associated, but not yet fused with the postsynaptic membrane. Electron microscopic analysis of these complexes indicates that Exo70 mediates AMPA receptor insertion directly within the postsynaptic density, rather than at extrasynaptic membranes. Therefore, we propose a molecular and anatomical model that dissects AMPA receptor sorting and synaptic delivery within the spine, and uncovers new functions of the exocyst at the postsynaptic membrane.
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Exocyst-mediated AMPA receptor targeting, insertion, and recycling are thought to be independent of Ral.
“exocystmediated AMPA receptor targeting, insertion, and recycling (Sans et al, 2003;Gerges et al, 2006;Mao et al, 2010) are thought to be independent of Ral.”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Gerges et al, 2006
The Introduction and Discussion describe exocyst-mediated AMPA receptor targeting and insertion, and the section on Sec8 describes its role in constitutive synaptic cycling. Neither those passages nor the searches for Ral and Ral GTPase establish that these processes are independent of Ral. (LLM, conf=0.82)
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- Authors
- Gerges, N. Z., Backos, D. S., Rupasinghe, C. N., Spaller, M. R., & Esteban, J. A.
- Affiliations
- University of Michigan (US)
- Wayne State University (US)
- ORCID
- Backos, Donald S
- Venue
- The EMBO Journal
- Published
- 2006-04-06
- Volume
- 25
- Issue
- 8
- Pages
- 1623-1634
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1440842
- OpenAlex
- W2100449908
- Cited by
- 147
- References
- 8
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 11 · 2013: 11 · 2012: 6
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Mental Health (MH070417, R01MH070417)
- National Institute of General Medical Sciences (GM63032)
- 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 › Extracellular vesicles in disease
- Keywords
- exocyst complex, Sec8, Exo70, AMPA receptors, synaptic targeting, glutamate receptor trafficking, postsynaptic density, dendritic spines, excitatory synapses
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Hippocampus, Membrane Fusion, Membrane Proteins, Mutation, Synaptic Transmission, Neurons, Organ Culture Techniques, Synapses, Synaptic Membranes, Synaptosomes, Receptors, AMPA, Patch-Clamp Techniques, Protein Transport, Vesicular Transport Proteins, Dendritic Spines, Mice, Rats
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