| First Author | Brockhaus J | Year | 2024 |
| Journal | Cells | Volume | 13 |
| Issue | 11 | PubMed ID | 38891114 |
| Mgi Jnum | J:349905 | Mgi Id | MGI:7659371 |
| Doi | 10.3390/cells13110981 | Citation | Brockhaus J, et al. (2024) Conditional Knockout of Neurexins Alters the Contribution of Calcium Channel Subtypes to Presynaptic Ca(2+) Influx. Cells 13(11) |
| abstractText | Presynaptic Ca(2+) influx through voltage-gated Ca(2+) channels (VGCCs) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca(2+) influx via all VGCC subtypes similarly. Here, we performed live cell imaging of synaptic boutons from primary hippocampal neurons with a Ca(2+) indicator. We used the expression of inactive and active Cre recombinase to compare control to conditional knockout neurons lacking either all or selected neurexin variants. We found that reduced total presynaptic Ca(2+) transients caused by the deletion of all neurexins were primarily due to the reduced contribution of P/Q-type VGCCs. The deletion of neurexin1alpha alone also reduced the total presynaptic Ca(2+) influx but increased Ca(2+) influx via N-type VGCCs. Moreover, we tested whether the decrease in Ca(2+) influx induced by activation of cannabinoid receptor 1 (CB1-receptor) is modulated by neurexins. Unlike earlier observations emphasizing a role for beta-neurexins, we found that the decrease in presynaptic Ca(2+) transients induced by CB1-receptor activation depended more strongly on the presence of alpha-neurexins in hippocampal neurons. Together, our results suggest that neurexins have unique roles in the modulation of presynaptic Ca(2+) influx through VGCC subtypes and that different neurexin variants may affect specific VGCCs. |
