Toonen Ruud F G, Wierda Keimpe, Sons Michèle S, de Wit Heidi, Cornelisse L Niels, Brussaard Arjen, Plomp Jaap J, Verhage Matthijs
Department of Functional Genomics, Vrije Universiteit, De Boelelaan 1087, 1081 HV, Amsterdam, The Netherlands.
Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18332-7. doi: 10.1073/pnas.0608507103. Epub 2006 Nov 16.
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.
剧烈活动后的迅速恢复是大多数哺乳动物突触的一个基本特征。我们在此表明,突触前基因munc18-1表达降低的突触在谷氨酸能、γ-氨基丁酸能和神经肌肉突触的强烈刺激期间会出现增强的抑制。相反,munc18-1的过表达使这些突触恢复得更快。我们发现了可快速释放囊泡池及其再填充动力学的相应变化。停靠在活性区的囊泡数量和每个终末的囊泡总数与munc18-1表达水平以及可释放囊泡池的大小相关。这些数据表明,单个基因表达的变化通过调节停靠的、准备好释放的囊泡数量,从而调节分泌能力的补充来控制突触恢复。