| First Author | Lipstein N | Year | 2021 |
| Journal | Neuron | Volume | 109 |
| Issue | 24 | Pages | 3980-4000.e7 |
| PubMed ID | 34706220 | Mgi Jnum | J:325344 |
| Mgi Id | MGI:6877256 | Doi | 10.1016/j.neuron.2021.09.054 |
| Citation | Lipstein N, et al. (2021) Munc13-1 is a Ca(2+)-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission. Neuron 109(24):3980-4000.e7 |
| abstractText | During ongoing presynaptic action potential (AP) firing, transmitter release is limited by the availability of release-ready synaptic vesicles (SVs). The rate of SV recruitment (SVR) to release sites is strongly upregulated at high AP frequencies to balance SV consumption. We show that Munc13-1-an essential SV priming protein-regulates SVR via a Ca(2+)-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca(2+)-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca(2+)-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca(2+)-phospholipid binding has the opposite effects. Thus, Ca(2+)-phospholipid binding to the Munc13-1-C2B domain accelerates SVR, reduces short-term synaptic depression, and increases the endurance and temporal fidelity of neurotransmission, demonstrating that Munc13-1 is a core vesicle priming hub that adjusts SV re-supply to demand. |
