| First Author | Kim H | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 27 | Pages | 9244-9262 |
| PubMed ID | 32434929 | Mgi Jnum | J:291190 |
| Mgi Id | MGI:6445033 | Doi | 10.1074/jbc.RA120.013077 |
| Citation | Kim H, et al. (2020) Calsyntenin-3 interacts with both alpha- and beta-neurexins in the regulation of excitatory synaptic innervation in specific Schaffer collateral pathways. J Biol Chem 295(27):9244-9262 |
| abstractText | Calsyntenin-3 (Clstn3) is a postsynaptic adhesion molecule that induces presynaptic differentiation via presynaptic neurexins (Nrxns), but whether Nrxns directly bind to Clstn3 has been a matter of debate. Here, using LC-MS/MS-based protein analysis, confocal microscopy, RNAscope assays, and electrophysiological recordings, we show that beta-Nrxns directly interact via their LNS domain with Clstn3 and Clstn3 cadherin domains. Expression of splice site 4 (SS4) insert-positive beta-Nrxn variants, but not insert-negative variants, reversed the impaired Clstn3 synaptogenic activity observed in Nrxn-deficient neurons. Consistently, Clstn3 selectively formed complexes with SS4-positive Nrxns in vivo Neuron-specific Clstn3 deletion caused significant reductions in number of excitatory synaptic inputs. Moreover, expression of Clstn3 cadherin domains in CA1 neurons of Clstn3 conditional knockout mice rescued structural deficits in excitatory synapses, especially within the stratum radiatum layer. Collectively, our results suggest that Clstn3 links to SS4-positive Nrxns to induce presynaptic differentiation and orchestrate excitatory synapse development in specific hippocampal neural circuits, including Schaffer collateral afferents. |
