Trans-synaptic interaction of GluRδ2 and neurexin through Cbln1 mediates synapse formation in the cerebellum
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Elucidation of molecular mechanisms that regulate synapse formation is required for the understanding of neural wiring, higher brain functions, and mental disorders. Despite the wealth of in vitro information, fundamental questions about how glutamatergic synapses are formed in the mammalian brain remain unanswered. Glutamate receptor (GluR) delta2 is essential for cerebellar synapse formation in vivo. Here, we show that the N-terminal domain (NTD) of GluRdelta2 interacts with presynaptic neurexins (NRXNs) through cerebellin 1 precursor protein (Cbln1). The synaptogenic activity of GluRdelta2 is abolished in cerebellar primary cultures from Cbln1 knockout mice and is restored by recombinant Cbln1. Knockdown of NRXNs in cerebellar granule cells also hinders the synaptogenic activity of GluRdelta2. Both the NTD of GluRdelta2 and the extracellular domain of NRXN1beta suppressed the synaptogenic activity of Cbln1 in cerebellar primary cultures and in vivo. These results suggest that GluRdelta2 mediates cerebellar synapse formation by interacting with presynaptic NRXNs through Cbln1.
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Differential adhesion mediated by neurexins and cerebellins is required for synapse formation and function.
“differential adhesion mediated by neurexins and cerebellins is required for synapse formation and function”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Uemura et al., 2010
Regulation of Nrxn exon 20 generates AS4+ or AS4- isoforms that show differential binding to cell-type-specific postsynaptic partners.
“Regulation of Nrxn exon 20 generates AS4+ or AS4– isoforms that show differential binding to cell-type-specific postsynaptic partners88,92.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [92]
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Jones, R. M., Cadby, G., Melton, P. E., Abraham, L. J., Whitehouse, A. J., & Moses, E. K. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00658 · Cited by 33 · see citing works
Social behavior in prepubertal neurexin 1α deficient rats: A model of neurodevelopmental disorders.
Kight, K. E., Argue, K. J., Bumgardner, J. G., Bardhi, K., Waddell, J., & McCarthy, M. M. (2021) · Behavioral Neuroscience · doi:10.1037/bne0000482 · Cited by 17 · see citing works
Neurexin‐β mediates the synaptogenic activity of amyloid precursor protein
Cvetkovska, V., Ge, Y., Xu, Q., Li, S., Zhang, P., & Craig, A. M. (2022) · The Journal of Neuroscience · doi:10.1523/jneurosci.0511-21.2022 · Cited by 17 · see citing works
Synaptic Organizers in Alzheimer’s Disease: A Classification Based on Amyloid-β Sensitivity
Lee, A. K., Khaled, H., Chofflet, N., & Takahashi, H. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00281 · Cited by 14 · see citing works
- Authors
- Uemura, T., Lee, S.-J., Yasumura, M., Takeuchi, T., Yoshida, T., Ra, M., Taguchi, R., Sakimura, K., & Mishina, M.
- Affiliations
- The University of Tokyo (JP)
- Brain Research Institute, Niigata University (JP)
- Corresponding author
- Mishina, Masayoshi
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 141
- Issue
- 6
- Pages
- 1068-1079
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2057569198
- Cited by
- 496
- References
- 65
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 21 · 2023: 27 · 2022: 22 · 2021: 43 · 2020: 36 · 2019: 24 · 2018: 29 · 2017: 28 · 2016: 40 · 2015: 34 · 2014: 30 · 2013: 29 · 2012: 32
- FWCI
- 13.94
- 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, 1173 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)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- GluRdelta2, neurexin, Cbln1, synaptogenesis, glutamatergic synapses, cerebellar granule cells, N-terminal domain
- MeSH terms
- Animals, Calcium-Binding Proteins, Cell Line, Cells, Cultured, Cerebellum, Humans, Nerve Tissue Proteins, Protein Precursors, Synapses, Receptors, Glutamate, Neural Cell Adhesion Molecules, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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