| First Author | Lin PY | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 13 | Pages | e2300363120 |
| PubMed ID | 36961922 | Mgi Jnum | J:346435 |
| Mgi Id | MGI:7461058 | Doi | 10.1073/pnas.2300363120 |
| Citation | Lin PY, et al. (2023) Neurexin-2 restricts synapse numbers and restrains the presynaptic release probability by an alternative splicing-dependent mechanism. [RETRACTED]. Proc Natl Acad Sci U S A 120(13):e2300363120 |
| abstractText | alpha- and beta-neurexins are extensively alternatively spliced, presynaptic cell-adhesion molecules that are thought to organize synapse assembly. However, recent data revealed that, in the hippocampus in vivo, the deletion of one neurexin isoform, Nrxn2, surprisingly increased excitatory synapse numbers and enhanced their presynaptic release probability, suggesting that Nrxn2 restricts, instead of enabling, synapse assembly. To delineate the synaptic function and mechanism of action of Nrxn2, we examined cultured hippocampal neurons as a reduced system. In heterologous synapse formation assays, different alternatively spliced Nrxn2beta isoforms robustly promoted synapse assembly similar to Nrxn1beta and Nrxn3beta, consistent with a general synaptogenic function of neurexins. Deletion of Nrxn2 from cultured hippocampal neurons, however, caused a significant increase in synapse density and release probability, replicating the in vivo data that suggested a synapse-restricting function. Rescue experiments revealed that two of the four Nrxn2beta splice variants (Nrxn2beta-SS4+/SS5- and Nrxn2beta-SS4+/SS5+) reversed the increase in synapse density in Nrxn2-deficient neurons, whereas only one of the four Nrxn2beta splice variants (Nrxn2beta-SS4+/SS5+) normalized the increase in release probability in Nrxn2-deficient neurons. Thus, a subset of Nrxn2 splice variants restricts synapse numbers and restrains their release probability in cultured neurons. |
