4.7 Article

Presynaptic Short-Term Plasticity Persists in the Absence of PKC Phosphorylation of Munc18-1

期刊

JOURNAL OF NEUROSCIENCE
卷 41, 期 35, 页码 7329-7339

出版社

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0347-21.2021

关键词

Munc18-1; PKC; plasticity; post-tetanic potentiation; synapse

资金

  1. National Institutes of Health [R01-NS-032405, R35-NS-097284, R01-NS-083898]
  2. Goldenson Fellowship
  3. Boehringer Ingelheim Fonds PhD Fellowship
  4. B&C Privatstiftung Forschungsforderung
  5. Alice and Joseph Brooks Postdoctoral Fellowship

向作者/读者索取更多资源

The study found that even with the elimination of PKC phosphorylation sites on Munc18-1, synaptic transmission between hippocampal and cerebellar neurons can still be enhanced through other mechanisms, including PTP. This suggests that PKC regulation is not the sole factor affecting neuronal conduction.
Post-tetanic potentiation (PTP) is a form of short-term plasticity that lasts for tens of seconds following a burst of presynaptic activity. It has been proposed that PTP arises from protein kinase C (PKC) phosphorylation of Munc18-1, an SM (Sec1/ Munc-18 like) family protein that is essential for release. To test this model, we made a knock-in mouse in which all Munc18-1 PKC phosphorylation sites were eliminated through serine-to-alanine point mutations (Munc18-1SA mice), and we studied mice of either sex. The expression of Munc18-1 was not altered in Munc18-1SA mice, and there were no obvious behavioral phenotypes. At the hippocampal CA3-to-CA1 synapse and the granule cell parallel fiber (PF)-to-Purkinje cell (PC) synapse, basal transmission was largely normal except for small decreases in paired-pulse facilitation that are consistent with a slight elevation in release probability. Phorbol esters that mimic the activation of PKC by diacylglycerol still increased synaptic transmission in Munc18-1SA mice. In Munc18-1SA mice, 70% of PTP remained at CA3-to-CA1 synapses, and the amplitude of PTP was not reduced at PF-to-PC synapses. These findings indicate that at both CA3-to-CA1 and PF-to-PC synapses, phorbol esters and PTP enhance synaptic transmission primarily by mechanisms that are independent of PKC phosphorylation of Munc18-1.

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