Munc18-1 is a dynamically regulated PKC target during short-term enhancement of transmitter release

eLife

Ralf Schneggenburger¹  Ruud F Toonen²  Matthijs Verhage²  Olexiy Kochubey³  Özgür Genç³ 

[1] Department of Genetics, VU University Medical Center, VU University, Amsterdam, Netherlands;Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Amsterdam, Netherlands;Laboratory of Synaptic Mechanisms, Brain Mind Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;

关键词: synaptic plasticity;    transmitter release;    protein kinase C;    protein phosphatase;    calyx of Held;    synaptic transmission;   

DOI  :  10.7554/eLife.01715

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown