Emerging roles of the neurotrophin receptor TrkC in synapse organization. (March 2017)

• Record Type: Journal Article
• Authors: Naito, Yusuke; Lee, Alfred Kihoon; Takahashi, Hideto
• Is Part Of: Neuroscience research. Volume 116(2017:Mar.)
• Page Start: 10
• Page End: 17
• Publication Date: 2017-03
• Subjects: TrkC -- PTPσ -- Neurotrophin-3 -- Synapse organizer -- Fibroblast-neuron co-culture -- Synaptogenesis -- Synapse competition -- Neuropsychiatric disorders; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2016.09.009
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: An unbiased cDNA screen isolated TrkC as a synaptogenic cell adhesion molecule. Postsynaptic TrkC interacts with presynaptic PTPσ. TrkC–PTPσ complex has bidirectional synaptogenic activity for excitatory synapses. NT-3 modulates excitatory presynapse induction activity of TrkC. 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.