| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5738996 | Neuroscience Research | 2017 | 8 Pages |
â¢An unbiased cDNA screen isolated TrkC as a synaptogenic cell adhesion molecule.â¢Postsynaptic TrkC interacts with presynaptic PTPÏ.â¢TrkC-PTPÏ complex has bidirectional synaptogenic activity for excitatory synapses.â¢NT-3 modulates excitatory presynapse induction activity of TrkC.
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 (PTPÏ). TrkC-PTPÏ specifically induces excitatory synapses in a kinase domain-independent manner. TrkC has distinct extracellular domains for PTPÏ- and NT-3-binding and thus may bind both ligands simultaneously. Indeed, NT-3 enhances the TrkC-PTPÏ 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-PTPÏ complex as well as competitive modulation of TrkC-mediated synaptogenesis by heparan sulfate proteoglycans (HSPGs), which bind the same domain of TrkC as PTPÏ. Thus, there is strong evidence supporting a role for the TrkC-PTPÏ complex in mechanisms underlying the fine turning of neural connectivity. Furthermore, disruption of the TrkC-PTPÏ 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.
