Spatial regulation of an E3 ubiquitin ligase directs selective synapse elimination
Spatial regulation of an E3 ubiquitin ligase directs selective synapse elimination
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DOI：
10.1126/science.1145727
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发表时间：
2007-08-17
期刊：
影响因子：
56.9
通讯作者：
Shen, Kang
中科院分区：
文献类型：
--
作者：
Ding, Mei;Chao, Dan;Shen, Kang
定型的突触连接可以通过突触发生过程中合适的伙伴之间的精确识别和选择性突触消除来产生。选择性去除突触的分子机制在很大程度上是未知的。我们发现，定型发育消除的秀丽隐杆线虫雌雄同体特异性运动神经元（HSNL）的突触介导的E3泛素连接酶，Skp 1-cullin-F-box（SCF）的SKR-1和F-盒蛋白SEL-10组成的复合物。突触粘附分子SYG-1与SKR-1结合，抑制SCF复合物的组装，从而保护附近的突触。因此，泛素介导的蛋白质降解的亚细胞调节通过选择性突触消除有助于精确的突触连接。
Stereotyped synaptic connectivity can arise both by precise recognition between appropriate partners during synaptogenesis and by selective synapse elimination. The molecular mechanisms that underlie selective synapse removal are largely unknown. We found that stereotyped developmental elimination of synapses in the Caenorhabditis elegans hermaphrodite-specific motor neuron (HSNL) was mediated by an E3 ubiquitin ligase, a Skp1-cullin-F-box (SCF) complex composed of SKR-1 and the F-box protein SEL-10. SYG-1, a synaptic adhesion molecule, bound to SKR-1 and inhibited assembly of the SCF complex, thereby protecting nearby synapses. Thus, subcellular regulation of ubiquitin-mediated protein degradation contributes to precise synaptic connectivity through selective synapse elimination.