Muncl 8-1 redistributes in nerve terminals in an activity- and PKC-dependent manner

T. Cijsouw, J.P. Weber, J.H.P. Broeke, J.A. Broek, D. Schut, T. Kroon, I. Saarloos, M. Verhage, R.F.G. Toonen

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)

Abstract

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. © 2014 Cijsouw et al.
Original languageEnglish
Pages (from-to)759-775
JournalJournal of cell biology
Volume204
Issue number5
DOIs
Publication statusPublished - 2014

Cite this