Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size

被引:135
作者
Toonen, Ruud F. G.
Wierda, Keirnpe
Sons, Michele S.
de Wit, Heidi
Cornelisse, L. Niels
Brussaard, Arjen
Plomp, Jaap J.
Verhage, Matthijs
机构
[1] Free Univ Amsterdam, Dept Funct Genom, Ctr Neurogenet & Cognit Res, NL-1081 HV Amsterdam, Netherlands
[2] Free Univ Amsterdam, Dept Expt Neurophysiol, Ctr Neurogenet & Cognit Res, NL-1081 HV Amsterdam, Netherlands
[3] Leiden Univ, Ctr Med, Dept Neurol, NL-2300 RC Leiden, Netherlands
[4] Leiden Univ, Ctr Med, Dept Neurophysiol, NL-2300 RC Leiden, Netherlands
[5] Univ Utrecht, Med Ctr, Rudolf Magnus Inst Neurosci, Dept Pharmacol & Anat, NL-3584 CG Utrecht, Netherlands
关键词
autapse; docking; exocytosis; secretion; synaptic transmission;
D O I
10.1073/pnas.0608507103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Prompt recovery after intense activity is an essential feature of most mammalian synapses. Here we show that synapses with reduced expression of the presynaptic gene munc18-1 suffer from increased depression during intense stimulation at glutamatergic, GABAergic, and neuromuscular synapses. Conversely, munc18-1 overexpression makes these synapses recover faster. Concomitant changes in the readily releasable vesicle pool and its refill kinetics were found. The number of vesicles docked at the active zone and the total number of vesicles per terminal correlated with both munc18-1 expression levels and the size of the releasable vesicle pool. These data show that varying expression of a single gene controls synaptic recovery by modulating the number of docked, release-ready vesicles and thereby replenishment of the secretion capacity.
引用
收藏
页码:18332 / 18337
页数:6
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