E3 ubiquitin ligase RNF13 involves spatial learning and assembly of the SNARE complex

E3 ubiquitin ligase RNF13 involves spatial learning and assembly of the SNARE complex
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E3 泛素连接酶 RNF13 涉及 SNARE 复合体的空间学习和组装

DOI:
10.1007/s00018-012-1103-5
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发表时间:
2012-08
影响因子:
8
通讯作者:
Zhu, Dahai
Zhu, Dahai
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang, Lei;Yang, Nan;Meng, Jiao;Zuo, Pingping;Zhang, Yong;Chen, Jie;Wang, Li;Gao, Xiang;Zhu, Dahai

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突触的结构和数量的变化调节学习、记忆以及认知障碍。泛素介导的蛋白质修饰是调节突触活动的一个关键机制,尽管对这一过程的精确调控仍知之甚少。
Changes in the structure and number of synapses modulate learning, memory and cognitive disorders. Ubiquitin-mediated protein modification is a key mechanism for regulating synaptic activity, though the precise control of this process remains poorly understood. RING finger protein 13 (RNF13) is a recently identified E3 ubiquitin ligase, and its in vivo function remains completely unknown. We show here that genetic deletion of RNF13 in mice leads to a significant deficit in spatial learning as determined by the Morris water maze test and Y-maze learning test. At the ultrastructral level, the synaptic vesicle density was decreased and the area of the active zone was increased at hippocampal synapses of RNF13-null mice compared with those of wild-type littermates. We found no change in the levels of SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex proteins in the hippocampus of RNF13-null mice, but impaired SNARE complex assembly. RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.
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