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Cited by 250Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersAxon Guidance and Neuronal Signaling

Selective control of inhibitory synapse development by Slitrk3-PTPδ trans-synaptic interaction

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Takahashi, Hideto, Katayama, Kei-ichi, Sohya, Kazuhiro, Miyamoto, Hiroyuki, Prasad, Tuhina, Matsumoto, Yoshifumi, Ota, Maya, Yasuda, Hiroki +3 more·2012·Nature Neuroscience
DOI 10.1038/nn.3040PMC PMC3288805
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Abstract

Balanced development of excitatory and inhibitory synapses is required for normal brain function, and an imbalance in this development may underlie the pathogenesis of many neuropsychiatric disorders. Compared with the many identified trans-synaptic adhesion complexes that organize excitatory synapses, little is known about the organizers that are specific for inhibitory synapses. We found that Slit and NTRK-like family member 3 (Slitrk3) actS as a postsynaptic adhesion molecule that selectively regulates inhibitory synapse development via trans-interaction with axonal tyrosine phosphatase receptor PTPδ. When expressed in fibroblasts, Slitrk3 triggered only inhibitory presynaptic differentiation in contacting axons of co-cultured rat hippocampal neurons. Recombinant Slitrk3 preferentially localized to inhibitory postsynaptic sites. Slitrk3-deficient mice exhibited decreases in inhibitory, but not excitatory, synapse number and function in hippocampal CA1 neurons and exhibited increased seizure susceptibility and spontaneous epileptiform activity. Slitrk3 required trans-interaction with axonal PTPδ to induce inhibitory presynaptic differentiation. These results identify Slitrk3-PTPδ as an inhibitory-specific trans-synaptic organizing complex that is required for normal functional GABAergic synapse development.

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  • SLITRK3 is a neurotrophin receptor required for normal GABAergic synapse development.

    “A third neurotrophin receptor required for normal GABAergic synapse development, SLITRK383, is also downregulated (Fig. 4m).”

    From Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation (2017) · cites this paper as [83]

    The Abstract and Discussion identify Slitrk3 as required for normal functional GABAergic synapse development. They describe it as a postsynaptic adhesion molecule, however, not a neurotrophin receptor; the receptor identified for its trans-synaptic interaction is PTPδ. No page numbers are available in our copy. (LLM, conf=0.88)

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Authors
Takahashi, H., Katayama, K.-I., Sohya, K., Miyamoto, H., Prasad, T., Matsumoto, Y., Ota, M., Yasuda, H., Tsumoto, T., Aruga, J., & Craig, A. M.
Affiliations
  • University of British Columbia (CA)
  • Japan Science and Technology Agency (JP)
  • RIKEN Center for Brain Science (JP)
  • Gunma University (JP)
  • RIKEN (JP)
Corresponding author
  • Aruga, Jun
  • Craig, Ann Marie
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2012-01-29
Volume
15
Issue
3
Pages
389-398
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn.3040
PMC
PMC3288805
OpenAlex
W2074369549
Cited by
250
References
4
Citations by year
2026: 11 · 2025: 16 · 2024: 18 · 2023: 11 · 2022: 13 · 2021: 14 · 2020: 20 · 2019: 15 · 2018: 23 · 2017: 18 · 2016: 27 · 2015: 16 · 2014: 21 · 2013: 23 · 2012: 3
FWCI
8.30
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Canadian Institutes of Health Research (MOP84241)
  • Japan Society for the Promotion of Science (23500461, 21200016, 21240031)
  • National Institute of Mental Health (MH-070860, R01MH070860)
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 › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
excitation-inhibition balance, GABAergic synapses, presynaptic differentiation, CA1 pyramidal neurons, seizure susceptibility, epilepsy, synaptic development
MeSH terms
Animals, Animals, Newborn, Brain, Cell Differentiation, Cells, Cultured, Chlorocebus aethiops, Disease Models, Animal, Electroencephalography, Epilepsy, Female, Gene Expression Regulation, Glutamate Decarboxylase, Humans, Luminescent Proteins, Male, Membrane Proteins, Mice, Inbred C57BL, Nerve Tissue Proteins, Neural Inhibition, Synaptic Transmission, Protein Binding, Synapses, Transfection, Cell Adhesion Molecules, Presynaptic Terminals, Mice, Knockout, Coculture Techniques, RNA, Small Interfering, Vesicular Inhibitory Amino Acid Transport Proteins, Vesicular Glutamate Transport Protein 1, Mice, Rats, Inhibitory Postsynaptic Potentials, Receptor-Like Protein Tyrosine Phosphatases, Class 2

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