Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes
Open accessAbstract
Dendritic spines are micron-sized membrane protrusions receiving most excitatory synaptic inputs in the mammalian brain. Spines form and grow during long-term potentiation (LTP) of synaptic strength. However, the source of membrane for spine formation and enlargement is unknown. Here we report that membrane trafficking from recycling endosomes is required for the growth and maintenance of spines. Using live-cell imaging and serial section electron microscopy, we demonstrate that LTP-inducing stimuli promote the mobilization of recycling endosomes and vesicles into spines. Preventing recycling endosomal transport abolishes LTP-induced spine formation. Using a pH-sensitive recycling cargo, we show that exocytosis from recycling endosomes occurs locally in spines, is triggered by activation of synaptic NMDA receptors, and occurs concurrently with spine enlargement. Thus, recycling endosomes provide membrane for activity-dependent spine growth and remodeling, defining a novel membrane trafficking mechanism for spine morphological plasticity and providing a mechanistic link between structural and functional plasticity during LTP.
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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 Park et al., 2006
Exocytic trafficking from recycling compartments contributes to dendritic spine growth in response to activity.
“Exocytic trafficking from recycling compartments contributes to dendritic spine growth in response to activity (Park et al, 2006;Kennedy et al, 2010)”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Park et al, 2006
LTP increases spine volume, a process that requires the addition of membranes whose source remains largely unknown.
“In particular, LTP increases spine volume, a process that requires the addition of membranes whose source remains largely unknown”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Park et al, 2006
Cites
Long-Term Potentiation--A Decade of Progress?
Malenka, R. C., & Nicoll, A. R. A. (1999) · Science · doi:10.1126/science.285.5435.1870 · Cited by 2,729 · see citing works
Structural basis of long-term potentiation in single dendritic spines
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. R., & Kasai, H. (2004) · Nature · doi:10.1038/nature02617 · Cited by 2,500 · see citing works
Matsuzaki, M., Ellis-Davies, G. C. R., Nemoto, T., Miyashita, Y., Iino, M., & Kasai, H. (2001) · Nature Neuroscience · doi:10.1038/nn736 · Cited by 1,563 · cited 3× · see citing works
“Such intimately coupled AMPA receptor insertion and membrane addition from recycling endosomes may help explain the tightly correlated scaling of spine size with AMPA receptor-mediated synaptic currents (Matsuzaki et al., 2001) and could plausibly account for the precise temporal relationship between spine enlargement…”
BackgroundInfluentialLong-term dendritic spine stability in the adult cortex
Grutzendler, J., Kasthuri, N., & Gan, W.-B. (2002) · Nature · doi:10.1038/nature01276 · Cited by 1,198 · cited 2× · see citing works
“Neuron 52, 817–830, December 7, 2006 ª2006 Elsevier Inc. DOI 10.1016/j.neuron.2006.09.040”
BackgroundInfluentialRapid Actin-Based Plasticity in Dendritic Spines
Fischer, M., Kaech, S., Knutti, D., & Matus, A. (1998) · Neuron · doi:10.1016/s0896-6273(00)80467-5 · Cited by 905 · see citing works
Recycling Endosomes Supply AMPA Receptors for LTP
Park, M., Penick, E. C., Edwards, J. G., Kauer, J. A., & Ehlers, M. D. (2004) · Science · doi:10.1126/science.1102026 · Cited by 730 · see citing works
Self-citationMerrifield, C. J., Perrais, D., & Zenisek, D. (2005) · Cell · doi:10.1016/j.cell.2005.03.015 · Cited by 476 · cited 2× · see citing works
“To directly visualize membrane delivery from recycling endosomes, we took advantage of a pH-sensitive variant of GFP (superecliptic pHluorin) whose fluorescence is quenched at low pH by fusing superecliptic pHluorin to the lumenal domain of the TfR (TfR-pHluorin) (Merrifield et al., 2005).”
BackgroundMethodIntegration of biochemical signalling in spines
Kennedy, M. B., Beale, H. C., Carlisle, H. J., & Washburn, L. R. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1685 · Cited by 286 · see citing works
Lang, C., Barco, A., Zablow, L., Kandel, E. R., Siegelbaum, S. A., & Zakharenko, S. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407581101 · Cited by 245 · see citing works
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Behzadi, S., Serpooshan, V., Tao, W., Hamaly, M. A., Alkawareek, M. Y., Dreaden, E. C., Brown, D., Alkilany, A. M., Farokhzad, O. C., & Mahmoudi, M. (2017) · Chemical Society Reviews · doi:10.1039/c6cs00636a · Cited by 2,859 · see citing works
Mechanisms of CaMKII action in long-term potentiation
Lisman, J., Yasuda, R., & Raghavachari, S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3192 · Cited by 1,134 · see citing works
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Morrow, E. M., Yoo, S.-Y., Flavell, S. W., Kim, T.-K., Lin, Y., Hill, R. S., Mukaddes, N. M., Balkhy, S., Gascon, G., Hashmi, A., et al. (2008) · Science · doi:10.1126/science.1157657 · Cited by 737 · see citing works
Ultrastructural evidence for synaptic scaling across the wake/sleep cycle
de Vivo, L., Bellesi, M., Marshall, W., Bushong, E. A., Ellisman, M. H., Tononi, G., & Cirelli, C. (2017) · Science · doi:10.1126/science.aah5982 · Cited by 574 · see citing works
AMPA Receptor Incorporation into Synapses during LTP: The Role of Lateral Movement and Exocytosis
Makino, H., & Malinow, R. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.035 · Cited by 501 · see citing works
The Subspine Organization of Actin Fibers Regulates the Structure and Plasticity of Dendritic Spines
Honkura, N., Matsuzaki, M., Noguchi, J., Ellis-Davies, G. C. R., & Kasai, H. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.013 · Cited by 490 · see citing works
Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines
Xie, Z., Srivastava, D. P., Photowala, H., Kai, L., Cahill, M. E., Woolfrey, K. M., Shum, C. Y., Surmeier, D. J., & Penzes, P. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.005 · Cited by 373 · see citing works
Soluble Aβ Inhibits Specific Signal Transduction Cascades Common to the Insulin Receptor Pathway
Townsend, M., Mehta, T., & Selkoe, D. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610390200 · Cited by 318 · see citing works
Bourne, J. N., & Harris, K. M. (2011) · Hippocampus · doi:10.1002/hipo.20768 · Cited by 318 · see citing works
Self-citationLocal protein synthesis, actin dynamics, and LTP consolidation
Bramham, C. R. (2008) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2008.09.013 · Cited by 301 · see citing works
Syntaxin-4 defines a domain for activity-dependent exocytosis in dendritic spines
Kennedy, M. J., Davison, I. G., Robinson, C. G., & Ehlers, M. D. (2010) · Cell · doi:10.1016/j.cell.2010.02.042 · Cited by 294 · see citing works
Self-citationRapid functional maturation of nascent dendritic spines
Zito, K., Scheuss, V., Knott, G., Hill, T., & Svoboda, K. (2009) · Neuron · doi:10.1016/j.neuron.2008.10.054 · Cited by 272 · see citing works
Chen, Y., Dubé, C. M., Rice, C. J., & Baram, T. Z. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0225-08.2008 · Cited by 276 · see citing works
Lu, J., Helton, T. D., Blanpied, T. A., Rácz, B., Newpher, T. M., Weinberg, R. J., & Ehlers, M. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.041 · Cited by 273 · see citing works
Self-citationChen, Y., Rex, C. S., Rice, C. J., Dubé, C. M., Gall, C. M., Lynch, G., & Baram, T. Z. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003825107 · Cited by 256 · see citing works
Patterson, M. A., Szatmari, E. M., & Yasuda, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913875107 · Cited by 259 · see citing works
Gilfillan, G. D., Selmer, K. K., Roxrud, I., Smith, R., Kyllerman, M., Eiklid, K., Kroken, M., Mattingsdal, M., Egeland, T., Stenmark, H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.01.013 · Cited by 232 · see citing works
Spine Expansion and Stabilization Associated with Long-Term Potentiation
Yang, Y., Wang, X.-B., Frerking, M., & Zhou, Q. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3998-07.2008 · Cited by 222 · see citing works
Biochemical Computation for Spine Structural Plasticity
Nishiyama, J., & Yasuda, R. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.043 · Cited by 199 · see citing works
A three-step model for the synaptic recruitment of AMPA receptors
Opazo, P., & Choquet, D. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2010.08.014 · Cited by 190 · see citing works
Plasticity of dendritic spines: subcompartmentalization of signaling
Colgan, L. A., & Yasuda, R. (2014) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170400 · Cited by 124 · see citing works
Keith, D. J., Sanderson, J. L., Gibson, E. S., Woolfrey, K. M., Robertson, H. R., Olszewski, K., Kang, R., El-Husseini, A., & Dell'Acqua, M. L. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0784-12.2012 · Cited by 108 · see citing works
Dendritic spine loss and neurodegeneration is rescued by Rab11 in models of Huntington's disease
Richards, P., Didszun, C., Campesan, S., Simpson, A., Horley, B., Young, K. W., Glynn, P., Cain, K., Kyriacou, C. P., Giorgini, F., et al. (2011) · Cell Death & Differentiation · doi:10.1038/cdd.2010.127 · Cited by 82 · see citing works
Molecular genetics and imaging technologies for circuit-based neuroanatomy
Arenkiel, B. R., & Ehlers, M. D. (2009) · Nature · doi:10.1038/nature08536 · Cited by 78 · see citing works
Self-citationBarriers in the brain: resolving dendritic spine morphology and compartmentalization
Adrian, M., Kusters, R., Wierenga, C. J., Storm, C., Hoogenraad, C. C., & Kapitein, L. C. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00142 · Cited by 62 · see citing works
“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).”
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Teodoro, R. O., Pekkurnaz, G., Nasser, A., Higashi‐Kovtun, M. E., Balakireva, M., McLachlan, I. G., Camonis, J., & Schwarz, T. L. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.147 · Cited by 61 · see citing works
Contreras, D., Piña, R., Carvallo, C., Godoy, F., Ugarte, G., Zeise, M., Rozas, C., & Morales, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137099 · Cited by 35 · see citing works
- Authors
- Park, M., Salgado, J. M., Ostroff, L., Helton, T. D., Robinson, C. G., Harris, K. M., & Ehlers, M. D.
- Affiliations
- Duke Medical Center (US)
- Augusta University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ehlers, Michael D.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 52
- Issue
- 5
- Pages
- 817-830
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC1899130
- OpenAlex
- W2135004571
- Cited by
- 493
- References
- 9
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 14 · 2023: 6 · 2022: 13 · 2021: 19 · 2020: 30 · 2019: 18 · 2018: 20 · 2017: 22 · 2016: 20 · 2015: 25 · 2014: 39 · 2013: 42 · 2012: 23
- FWCI
- 14.93
- 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, 2420 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)
- Funders
- American Health Assistance Foundation
- Raymond and Beverly Sackler Foundation (EB002170, NS21184, NS33574)
- 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
- dendritic spines, recycling endosomes, exocytosis, membrane trafficking, long-term potentiation, synaptic plasticity, NMDA receptor, synaptic vesicles
- MeSH terms
- Animals, Biological Transport, Active, DNA, Electrophysiology, Exocytosis, Hippocampus, Image Processing, Computer-Assisted, Immunohistochemistry, Microscopy, Electron, Neuronal Plasticity, Endosomes, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Microscopy, Electron, Transmission, Cell Size, Dendritic Spines, Rats
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