The Reelin signaling pathway promotes dendritic spine development in hippocampal neurons
Open accessAbstract
The development of distinct cellular layers and precise synaptic circuits is essential for the formation of well functioning cortical structures in the mammalian brain. The extracellular protein Reelin, through the activation of a core signaling pathway, including the receptors ApoER2 and VLDLR (very low density lipoprotein receptor) and the adapter protein Dab1 (Disabled-1), controls the positioning of radially migrating principal neurons, promotes the extension of dendritic processes in immature forebrain neurons, and affects synaptic transmission. Here we report for the first time that the Reelin signaling pathway promotes the development of postsynaptic structures such as dendritic spines in hippocampal pyramidal neurons. Our data underscore the importance of Reelin as a factor that promotes the maturation of target neuronal populations and the development of excitatory circuits in the postnatal hippocampus. These findings may have implications for understanding the origin of cognitive disorders associated with Reelin deficiency.
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ApoER2 mediates Reelin signaling to enhance learning and memory in mice.
“Since loss of ApoER2 impairs LTP, and since ApoER2 mediates Reelin signaling to enhance learning and memory in mice (Bosch et al., 2016; Niu et al., 2008; Rogers et al., 2011), it has been suggested that increased ApoER2 expression would be beneficial.”
From The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning (2017) · cites this paper as Niu et al., 2008
Exogenous recombinant Reelin recovers the dendritic spine deficit in cultured hippocampal slices from HRM and reeler mice and increases dendritic spine density in wild-type control slices.
“Exogenous recombinant Reelin recovers this deficit in cultured hippocampal slices from HRM and reeler mice as well as increases dendritic spine density in wild-type control slices (14).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [14]
ApoER2/VLDLR and both Dab1 and SFKs are essential for Reelin-mediated spinogenesis.
“The downstream signaling partners, ApoER2/VLDLR and both Dab1 and SFKs, are essential for this Reelin-mediated spinogenesis (14).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [14]
HRM and reeler hippocampal neurons have fewer dendritic spines along their dendrites compared with wild-type neurons, and the extent of this effect is proportional to the reduction in Reelin protein abundance.
“HRM and reeler hippocampal neurons have fewer dendritic spines along their dendrites when compared with wild-type neurons, and the extent of this effect is proportional to the reduction in Reelin protein abundance (14,15).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [14]
Postsynaptic compartments of both homozygous and heterozygous reeler synapses have a drastic and comparable reduction in the NR2A subunit of NMDAR and PSD-95 compared with wild-type synapses.
“The postsynaptic compartments of both homozygous and heterozygous reeler synapses have a drastic and comparable reduction in the NR2A subunit of the NMDAR and PSD-95 in comparison with wild-type synapses (14).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [14]
Reelin signaling is a critical regulator of both the number and strength of synaptic connections.
“The number of synaptic connections and the molecular composition of these compartments determine the efficacy of neuronal networks, and Reelin signaling is a critical regulator of both the number and the strength of these connections (14).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [14]
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Role for Reelin in neurotransmitter release
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Bosch, C., Masachs, N., Exposito-Alonso, D., Martínez, A., Teixeira, C. M., Fernaud, I., Pujadas, L., Ulloa, F., Comella, J. X., DeFelipe, J., et al. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw216 · Cited by 70 · see citing works
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ApoE receptor 2 regulates synapse and dendritic spine formation
Dumanis, S. B., Cha, H.-J., Song, J. M., Trotter, J. H., Spitzer, M., Lee, J.-Y., Weeber, E. J., Turner, R. S., Pak, D. T. S., Rebeck, G. W., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017203 · Cited by 45 · see citing works
Sorting nexin 17 regulates ApoER2 recycling and reelin signaling
Sotelo, P., Farfán, P., Benitez, M. L., Bu, G., & Marzolo, M.-P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093672 · Cited by 47 · see citing works
Reelin proteolysis affects signaling related to normal synapse function and neurodegeneration
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Laminar distribution of neurotransmitter receptors in different reeler mouse brain regions
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- Authors
- Niu, S., Yabut, O., & D'Arcangelo, G.
- Affiliations
- Baylor College of Medicine (US)
- Rutgers, The State University of New Jersey (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-10-08
- Volume
- 28
- Issue
- 41
- Pages
- 10339-10348
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2572775
- OpenAlex
- W2141654359
- Cited by
- 266
- References
- 62
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 6 · 2023: 13 · 2022: 19 · 2021: 15 · 2020: 17 · 2019: 11 · 2018: 9 · 2017: 16 · 2016: 24 · 2015: 11 · 2014: 24 · 2013: 20 · 2012: 14
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS042616)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Reelin signaling, dendritic spine development, hippocampal pyramidal neurons, ApoER2, VLDLR, Dab1, cognitive disorders
- MeSH terms
- Reelin Protein, Animals, Cells, Cultured, Hippocampus, Nerve Tissue Proteins, Receptors, LDL, Recombinant Proteins, Serine Endopeptidases, Signal Transduction, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Pyramidal Cells, Receptors, Lipoprotein, src-Family Kinases, LDL-Receptor Related Proteins, Dendritic Spines, Mice
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