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Postsynaptic Positioning of Endocytic Zones and AMPA Receptor Cycling by Physical Coupling of Dynamin-3 to Homer
Open accessAbstract
Endocytosis of AMPA receptors and other postsynaptic cargo occurs at endocytic zones (EZs), stably positioned sites of clathrin adjacent to the postsynaptic density (PSD). The tight localization of postsynaptic endocytosis is thought to control spine composition and regulate synaptic transmission. However, the mechanisms that situate the EZ near the PSD and the role of spine endocytosis in synaptic transmission are unknown. Here, we report that a physical link between dynamin-3 and the postsynaptic adaptor Homer positions the EZ near the PSD. Disruption of dynamin-3 or its interaction with Homer uncouples the PSD from the EZ, resulting in synapses lacking postsynaptic clathrin. Loss of the EZ leads to a loss of synaptic AMPA receptors and reduced excitatory synaptic transmission that corresponds with impaired synaptic recycling. Thus, a physical link between the PSD and the EZ ensures localized endocytosis and recycling by recapturing and maintaining a proximate pool of cycling AMPA receptors.
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“DNM3 participates in the morphogenesis of the postsynaptic density and excitatory synaptic transmission24”
From Locus for severity implicates CNS resilience in progression of multiple sclerosis (2023) · cites this paper as [24]
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Metadata
- Authors
- Lu, J., Helton, T. D., Blanpied, T. A., Rácz, B., Newpher, T. M., Weinberg, R. J., & Ehlers, M. D.
- Affiliations
- Duke Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ehlers, Michael D.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 55
- Issue
- 6
- Pages
- 874-889
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2597538
- OpenAlex
- W1997282555
- Cited by
- 273
- References
- 51
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 11 · 2020: 13 · 2019: 10 · 2018: 19 · 2017: 11 · 2016: 8 · 2015: 16 · 2014: 15 · 2013: 21 · 2012: 18
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2146 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- 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
- DNM3, Homer, postsynaptic density, clathrin, synaptic transmission, dendritic spine morphology, excitatory synapses, receptor recycling, protein-protein interaction
- MeSH terms
- Homer Scaffolding Proteins, Animals, Carrier Proteins, Clathrin, DNA, Electrophysiology, Humans, Immunohistochemistry, Microscopy, Electron, Synaptic Transmission, Neurons, Receptors, AMPA, Patch-Clamp Techniques, Microscopy, Confocal, GTP Phosphohydrolases, Transport Vesicles, Dynamin III, RNA Interference, Lipid Metabolism
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