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Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission
Neuron ( IF 14.7 ) Pub Date : 2017-08-31 00:00:00 , DOI: 10.1016/j.neuron.2017.08.016
Suneel Reddy-Alla , Mathias A. Böhme , Eric Reynolds , Christina Beis , Andreas T. Grasskamp , Malou M. Mampell , Marta Maglione , Meida Jusyte , Ulises Rey , Husam Babikir , Anthony W. McCarthy , Christine Quentin , Tanja Matkovic , Dominique Dufour Bergeron , Zeeshan Mushtaq , Fabian Göttfert , David Owald , Thorsten Mielke , Stefan W. Hell , Stephan J. Sigrist , Alexander M. Walter

Neural information processing depends on precisely timed, Ca2+-activated synaptic vesicle exocytosis from release sites within active zones (AZs), but molecular details are unknown. Here, we identify that the (M)Unc13-family member Unc13A generates release sites and show the physiological relevance of their restrictive AZ targeting. Super-resolution and intravital imaging ofDrosophilaneuromuscular junctions revealed that (unlike the other release factors Unc18 and Syntaxin-1A) Unc13A was stably and precisely positioned at AZs. Local Unc13A levels predicted single AZ activity. Different Unc13A portions selectively affected release site number, position, and functionality. An N-terminal fragment stably localized to AZs, displaced endogenous Unc13A, and reduced the number of release sites, while a C-terminal fragment generated excessive sites at atypical locations, resulting in reduced and delayed evoked transmission that displayed excessive facilitation. Thus, release site generation by the Unc13A C terminus and their specific AZ localization via the N terminus ensure efficient transmission and prevent ectopic, temporally imprecise release.

中文翻译:

Unc13的稳定位置将突触小泡融合限制在定义的释放位点,以促进同步神经传递。

神经信息处理取决于活动区域(AZ)内释放位点的精确定时的Ca2 +激活的突触囊泡胞吐作用,但分子细节尚不清楚。在这里,我们确定(M)Unc13家族成员Unc13A产生释放位点,并显示其限制性AZ靶向的生理相关性。果蝇神经肌肉接头的超分辨率和活体成像显示(与其他释放因子Unc18和Syntaxin-1A不同),Unc13A稳定且精确地位于AZ。本地Unc13A水平可预测单个AZ活性。Unc13A的不同部分有选择地影响了发布站点的编号,位置和功能。N端片段稳定地定位于AZ,取代了内源性Unc13A,并减少了释放位点的数量,而C末端片段在非典型位置产生了过多的位点,从而导致诱发传播的减少和延迟,从而显示出过度的促进作用。因此,Unc13A C末端的释放位点生成及其通过N末端的特定AZ定位可确保有效传递,并防止异位,时间不精确的释放。
更新日期:2017-09-20
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