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

Hideto Takahashi | Kei-Ichi Katayama | Kazuhiro Sohya | Hiroyuki Miyamoto | Tuhina Prasad | Yoshifumi Matsumoto | Maya Ota | Hiroki Yasuda | Tadaharu Tsumoto | Jun Aruga | Ann Marie Craig
Nature neuroscience | 2012

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.

Pubmed ID: 22286174

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R01 MH070860-08
  • Agency: NIMH NIH HHS, United States
    Id: MH070860
  • Agency: CIHR, Canada
    Id: MOP-84241
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH070860
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH070860-07

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