title: Emerging roles of the neurotrophin receptor TrkC in synapse organization.
abstract: Tropomyosin-receptor-kinase (Trk) receptors have been extensively studied for their roles in kinase-dependent signaling cascades in nervous system development. Synapse organization is coordinated by trans-synaptic interactions of various cell adhesion proteins, a representative example of which is the neurexin-neuroligin complex. Recently, a novel role for TrkC as a synapse organizing protein has been established. Post-synaptic TrkC binds to pre-synaptic type-IIa receptor-type protein tyrosine phosphatase sigma (PTPσ). TrkC-PTPσ specifically induces excitatory synapses in a kinase domain-independent manner. TrkC has distinct extracellular domains for PTPσ- and NT-3-binding and thus may bind both ligands simultaneously. Indeed, NT-3 enhances the TrkC-PTPσ interaction, thus facilitating synapse induction at the pre-synaptic side and increasing pre-synaptic vesicle recycling in a kinase-independent fashion. A crystal structure study has revealed the detailed structure of the TrkC-PTPσ complex as well as competitive modulation of TrkC-mediated synaptogenesis by heparan sulfate proteoglycans (HSPGs), which bind the same domain of TrkC as PTPσ. Thus, there is strong evidence supporting a role for the TrkC-PTPσ complex in mechanisms underlying the fine turning of neural connectivity. Furthermore, disruption of the TrkC-PTPσ complex may be the underlying cause of certain psychiatric disorders caused by mutations in the gene encoding TrkC (NTRK3), supporting its role in cognitive functions.
authors.affiliation: Synapse Development and Plasticity, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec H2W 1R7, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Synapse Development and Plasticity, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec H2W 1R7, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Alfred Kihoon
authors.initials: AK
authors.lastname: Lee
authors.affiliation: Synapse Development and Plasticity, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec H2W 1R7, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Quebec H3A 2B4, Canada; Department of Medicine, Université de Montréal, Montreal, Quebec H3T 1J4, Canada; Division of Experimental Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada. Electronic address: Hideto.Takahashi@ircm.qc.ca.
authors.forename: Hideto
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020933:Neurotrophin 3 / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
chemical_list: D020933:Neurotrophin 3; D017661:Receptors, Presynaptic; D020812:Receptor, trkC; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: Fibroblast-neuron co-culture; Neuropsychiatric disorders; Neurotrophin-3; PTPσ; Synapse competition; Synapse organizer; Synaptogenesis; TrkC