期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 70, 期 1, 页码 153-165出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-012-1103-5
关键词
RNF13; Ubiquitin ligase; Snapin; Synaptic vesicle; SNARE complex
资金
- National Basic Research Program of China [2005CB522405, 2005CB522500, 2007CB946903, 2009CB825403, 2006BAI23B00, 2006CB943500]
- National Natural Science Foundation of China [30721063, 30825024]
- Chinese National Programs for High Technology Research and Development [2006AA10A121, 2007AA02Z109]
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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