An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus
An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus
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一种替代剪接开关塑造了小鼠海马主要神经元与中间神经元中的神经素库
DOI：
10.7554/elife.22757
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发表时间：
2016
期刊：
影响因子：
7.7
通讯作者：
P. Scheiffele
中科院分区：
文献类型：
--
作者：
Thi;D. Schreiner;Le Xiao;Lisa Traunmüller;C. Bornmann;P. Scheiffele
主神经元和中间神经元群体的独特解剖和功能特征对于神经元回路的适当功能至关重要。细胞类型特异性特性由选择性基因表达程序编码，该程序形成分子库和突触蛋白复合物。然而，这些程序的性质，特别是在选择性剪接水平上的转录后调节，才刚刚开始出现。我们在这里证明，转录编码突触粘附分子neurexin-1，2，3通常在小鼠海马的主细胞和中间神经元表达，但经历高度差异，细胞类型特异性选择性剪接。主要的细胞特异性neurexin剪接异构体依赖于RNA结合蛋白Slm 2。相比之下，大多数小清蛋白阳性（PV+）中间神经元缺乏Slm 2，表达不同的neurexin剪接异构体，并共表达相应的剪接异构体特异性neurexin配体Cbln 4。在PV+细胞中选择性地进行Nrxn选择性剪接插入的条件性消融导致海马网络活性升高和学习任务受损。因此，神经毒素的PV细胞特异性选择性剪接对神经元回路功能至关重要http://dx.doi.org/10.7554/eLife.22757.001
The unique anatomical and functional features of principal and interneuron populations are critical for the appropriate function of neuronal circuits. Cell type-specific properties are encoded by selective gene expression programs that shape molecular repertoires and synaptic protein complexes. However, the nature of such programs, particularly for post-transcriptional regulation at the level of alternative splicing is only beginning to emerge. We here demonstrate that transcripts encoding the synaptic adhesion molecules neurexin-1,2,3 are commonly expressed in principal cells and interneurons of the mouse hippocampus but undergo highly differential, cell type-specific alternative splicing. Principal cell-specific neurexin splice isoforms depend on the RNA-binding protein Slm2. By contrast, most parvalbumin-positive (PV+) interneurons lack Slm2, express a different neurexin splice isoform and co-express the corresponding splice isoform-specific neurexin ligand Cbln4. Conditional ablation of Nrxn alternative splice insertions selectively in PV+ cells results in elevated hippocampal network activity and impairment in a learning task. Thus, PV-cell-specific alternative splicing of neurexins is critical for neuronal circuit function DOI: http://dx.doi.org/10.7554/eLife.22757.001
影响因子：
16.2
作者：
A. Boucard;Alexander A. Chubykin;D. Comoletti;P. Taylor;T. Südhof
通讯作者：
A. Boucard;Alexander A. Chubykin;D. Comoletti;P. Taylor;T. Südhof
影响因子：
13.9
作者：
Shen K;Scheiffele P
通讯作者：
Scheiffele P