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Postsynaptic TrkC and presynaptic PTPσ function as a bidirectional excitatory synaptic organizing complex.

Neuron | Jan 27, 2011

Neurotrophin receptor tyrosine kinases (Trks) have well-defined trophic roles in nervous system development through kinase activation by neurotrophins. Yet Trks have typical cell-adhesion domains and express noncatalytic isoforms, suggesting additional functions. Here we discovered noncatalytic TrkC in an unbiased hippocampal neuron-fibroblast coculture screen for proteins that trigger differentiation of neurotransmitter release sites in axons. All TrkC isoforms, but not TrkA or TrkB, function directly in excitatory glutamatergic synaptic adhesion by neurotrophin-independent high-affinity trans binding to axonal protein tyrosine phosphatase receptor PTPσ. PTPσ triggers and TrkC mediates clustering of postsynaptic molecules in dendrites, indicating bidirectional synaptic organizing functions. Effects of a TrkC-neutralizing antibody that blocks TrkC-PTPσ interaction and TrkC knockdown in culture and in vivo reveal essential roles of TrkC-PTPσ in glutamatergic synapse formation. Thus, postsynaptic TrkC trans interaction with presynaptic PTPσ generates bidirectional adhesion and recruitment essential for excitatory synapse development and positions these signaling molecules at the center of synaptic pathways.

Pubmed ID: 21262467 RIS Download

Mesh terms: Animals | COS Cells | Cell Differentiation | Cells, Cultured | Cercopithecus aethiops | Coculture Techniques | Fibroblasts | Glutamic Acid | Hippocampus | Mice | Neurons | Patch-Clamp Techniques | Post-Synaptic Density | Presynaptic Terminals | Receptor, trkC | Receptor-Like Protein Tyrosine Phosphatases, Class 2 | Recombinant Fusion Proteins | Synapses

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Associated grants

  • Agency: NIMH NIH HHS, Id: MH070860
  • Agency: NIMH NIH HHS, Id: R01 MH070860-06
  • Agency: NIMH NIH HHS, Id: R01 MH070860
  • Agency: NIMH NIH HHS, Id: R01 MH070860-07
  • Agency: Canadian Institutes of Health Research, Id: MOP-12675
  • Agency: Canadian Institutes of Health Research, Id: MOP-84241

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