Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size.
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.
Toonen
Ruud F G
RF
Department of Functional Genomics, Vrije Universiteit, De Boelelaan 1087, 1081 HV, Amsterdam, The Netherlands.
Wierda
Keimpe
K
Sons
Michèle S
MS
de Wit
Heidi
H
Cornelisse
L Niels
LN
Brussaard
Arjen
A
Plomp
Jaap J
JJ
Verhage
Matthijs
M
D000818:Animals; D005786:Gene Expression Regulation; D006579:Heterozygote; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors
D051938:Munc18 Proteins