Cited by 496Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeuroinflammation and Neurodegeneration Mechanisms

Trans-synaptic interaction of GluRδ2 and neurexin through Cbln1 mediates synapse formation in the cerebellum

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Uemura, Takeshi, Lee, Sung-Jin, Yasumura, Misato, Takeuchi, Tomonori, Yoshida, Tomoyuki, Ra, Moonjin, Taguchi, Ryo, Sakimura, Kenji +1 more·2010·Cell

Abstract

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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Crossref · 10.1016/j.cell.2010.04.035

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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
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
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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