线虫全基因组RNAi筛选确定CAB-1为特异性调节致密核心囊泡分泌的因子

内分泌细胞和神经细胞通过释放激素和神经肽类物质来响应外界刺激,而这些物质的分泌,都是通过致密核心囊泡(dense core vesicle,DCV)来实现的.但是,现阶段关于DCV的生成、转运、释放的机制很大程度上是不清楚的.在本研究中,我们将线虫的排便行为和肠道分泌联系起来,并以此表型进行全基因组RNAi筛选,寻找调节DCV的新基因.我们成功筛选到了一些在肠道调节DCV生成或释放的基因.其中,CAB-1被确认为特异性调节DCV分泌的重要因子.在肠道中,cab-1突变会降低肠道DCV内容物的分泌,而在神经系统中,CAB-1的缺失也会导致DCV的标识物堆积在突触前,而突触囊泡(synaptic vesicle,SV)不受影响.

Whole Genome RNAi Screen in C. elegans Identifies CAB-1 as a Novel Regulator of DCV Secretion

The dense core vesicle (DCV) is a key organelle involved in the secretion of hormones and neuropeptides in endocrine cells and neurons in response to stimulation. However, the mechanisms underlying its biogenesis, trafficking and exocytosis remain largely unknown. In this study, to discover novel players functioning in DCV secretion, we performed a genome-wide RNAi screen in C. elegans by observing worm defecation behavior. A series of genes that function in the intestine to regulate DCV biogenesis or exocytosis were successfully identified, including CAB-1, which was further determined to be a specific regulator for DCV exocytosis. In the intestine, cab-1 mutation causes reduced secretion of intestinal DCV cargoes. In the nervous system, the loss of CAB-1 leads to the accumulation of DCV markers in the presynaptic region, but synaptic vesicles are not affected. This work demonstrates that CAB-1 is a regulatory factor specifically involved in DCV secretion.