Munc18-1 redistributes in nerve terminals in an activity- and PKC-dependent manner

J Cell Biol. 2014 Mar 3;204(5):759-75. doi: 10.1083/jcb.201308026.


Munc18-1 is a soluble protein essential for synaptic transmission. To investigate the dynamics of endogenous Munc18-1 in neurons, we created a mouse model expressing fluorescently tagged Munc18-1 from the endogenous munc18-1 locus. We show using fluorescence recovery after photobleaching in hippocampal neurons that the majority of Munc18-1 trafficked through axons and targeted to synapses via lateral diffusion together with syntaxin-1. Munc18-1 was strongly expressed at presynaptic terminals, with individual synapses showing a large variation in expression. Axon-synapse exchange rates of Munc18-1 were high: during stimulation, Munc18-1 rapidly dispersed from synapses and reclustered within minutes. Munc18-1 reclustering was independent of syntaxin-1, but required calcium influx and protein kinase C (PKC) activity. Importantly, a PKC-insensitive Munc18-1 mutant did not recluster. We show that synaptic Munc18-1 levels correlate with synaptic strength, and that synapses that recruit more Munc18-1 after stimulation have a larger releasable vesicle pool. Hence, PKC-dependent dynamic control of Munc18-1 levels enables individual synapses to tune their output during periods of activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Electrophysiology
  • Gene Knock-In Techniques
  • Mice
  • Munc18 Proteins / analysis*
  • Munc18 Proteins / metabolism
  • Presynaptic Terminals / metabolism*
  • Protein Kinase C / metabolism*
  • Protein Transport
  • Synapses / metabolism
  • Syntaxin 1 / metabolism


  • Munc18 Proteins
  • Stxbp1 protein, mouse
  • Syntaxin 1
  • Protein Kinase C