Lipstein, NoaChang, ShuwenLin, Kun-HanLópez Murcia, Francisco JoséNeher, ErwinTaschenberger, HolgerBrose, Nils2024-01-312024-01-312021-120896-6273https://hdl.handle.net/2445/206796During 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 Ca2+-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca2+-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca2+-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca2+-phospholipid binding has the opposite effects. Thus, Ca2+-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.29 p.application/pdfengcc-by-nc-nd (c) Lipstein, Noa et al, 2021http://creativecommons.org/licenses/by-nc-nd/4.0/SinapsiNeurotransmissióNeuroplasticitatSynapsesNeural transmissionNeuroplasticityinfo:eu-repo/semantics/article7259552024-01-31info:eu-repo/semantics/openAccess34706220