Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity
Open accessAbstract
Learning-related plasticity at excitatory synapses in the mammalian brain requires the trafficking of AMPA receptors and the growth of dendritic spines. However, the mechanisms that couple plasticity stimuli to the trafficking of postsynaptic cargo are poorly understood. Here we demonstrate that myosin Vb (MyoVb), a Ca2+-sensitive motor, conducts spine trafficking during long-term potentiation (LTP) of synaptic strength. Upon activation of NMDA receptors and corresponding Ca2+ influx, MyoVb associates with recycling endosomes (REs), triggering rapid spine recruitment of endosomes and local exocytosis in spines. Disruption of MyoVb or its interaction with the RE adaptor Rab11-FIP2 abolishes LTP-induced exocytosis from REs and prevents both AMPA receptor insertion and spine growth. Furthermore, induction of tight binding of MyoVb to actin using an acute chemical genetic strategy eradicates LTP in hippocampal slices. Thus, Ca2+-activated MyoVb captures and mobilizes REs for AMPA receptor insertion and spine growth, providing a mechanistic link between the induction and expression of postsynaptic plasticity.
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Recycling endosomes necessary for delivery and retrieval of receptors operate both close to the synapse, within the head of the spine and in the dendritic shaft.
“These endosomes, necessary for the delivery and the retrieval of receptors, have been found to operate both close to the synapse, within the head of the spine and in the dendritic shaft (Park et al., 2006; Wang et al., 2008).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Wang et al., 2008
The Results section, “MyoVb is Enriched in Dendritic Spines and Traffics with Spine Endosomes” (page unavailable), places recycling endosomes at spine bases, occasionally in spine heads, and in dendritic shafts. The Introduction says they support local AMPA-receptor cycling and that disrupting their trafficking blocks receptor insertion. The copy does not establish that these endosomes are necessary for receptor retrieval, so that part of the claim is unsupported. (LLM, conf=0.79)
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Retracted
- Authors
- Wang, Z., Edwards, J. G., Riley, N., Provance, D. W., Karcher, R., Li, X.-D., Davison, I. G., Ikebe, M., Mercer, J. A., Kauer, J. A., & Ehlers, M. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Brown University (US)
- McLaughlin Research Institute (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Ehlers, Michael D.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 135
- Issue
- 3
- Pages
- 535-548
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2585749
- OpenAlex
- W2014923822
- Cited by
- 470
- References
- 4
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 14 · 2023: 5 · 2022: 24 · 2021: 18 · 2020: 21 · 2019: 21 · 2018: 22 · 2017: 26 · 2016: 28 · 2015: 25 · 2014: 38 · 2013: 43 · 2012: 42
- FWCI
- 18.74
- 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, 1750 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
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R01AG024492)
- National Institute of Mental Health (R01MH064748)
- National Institute of Neurological Disorders and Stroke (R01NS047574, R01NS039402)
- 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 › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- MYO5B, recycling endosomes, AMPA receptor trafficking, postsynaptic plasticity, long-term potentiation, exocytosis, NMDA receptor, calcium signaling, actin, hippocampus, chemical genetics
- MeSH terms
- rab11 GTP-Binding Proteins, Animals, Calcium, Cell Line, Dendrites, Hippocampus, Humans, Mice, Inbred Strains, Neuronal Plasticity, Neurons, Endosomes, Synapses, Long-Term Potentiation, Receptors, AMPA, rab GTP-Binding Proteins, Myosin Type V, Dendritic Spines, Mice, Rats
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