TY - JOUR TI - Munc18-1 is a dynamically regulated PKC target during short-term enhancement of transmitter release AU - Genç, Özgür AU - Kochubey, Olexiy AU - Toonen, Ruud F AU - Verhage, Matthijs AU - Schneggenburger, Ralf A2 - Rosenmund, Christian VL - 3 PY - 2014 DA - 2014/02/11 SP - e01715 C1 - eLife 2014;3:e01715 DO - 10.7554/eLife.01715 UR - https://doi.org/10.7554/eLife.01715 AB - Transmitter release at synapses is regulated by preceding neuronal activity, which can give rise to short-term enhancement of release like post-tetanic potentiation (PTP). Diacylglycerol (DAG) and Protein-kinase C (PKC) signaling in the nerve terminal have been widely implicated in the short-term modulation of transmitter release, but the target protein of PKC phosphorylation during short-term enhancement has remained unknown. Here, we use a gene-replacement strategy at the calyx of Held, a large CNS model synapse that expresses robust PTP, to study the molecular mechanisms of PTP. We find that two PKC phosphorylation sites of Munc18-1 are critically important for PTP, which identifies the presynaptic target protein for the action of PKC during PTP. Pharmacological experiments show that a phosphatase normally limits the duration of PTP, and that PTP is initiated by the action of a ‘conventional’ PKC isoform. Thus, a dynamic PKC phosphorylation/de-phosphorylation cycle of Munc18-1 drives short-term enhancement of transmitter release during PTP. KW - synaptic plasticity KW - transmitter release KW - protein kinase C KW - protein phosphatase KW - calyx of Held KW - synaptic transmission JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -