PDF(Pubmed)
Abstract：
In Caenorhabditis elegans, rhythmic posterior body wall muscle contractions mediate the highly regular defecation cycle. These contractions are regulated by inositol-1,4,5-trisphosphate (InsP3) receptor-dependent Ca2+ oscillations in intestinal epithelial cells. Here, we find that mutations in dec-7, which encodes the nematode ortholog of the human Sushi domain-containing 2 protein (SUSD2), lead to an increase in InsP3 receptor-dependent rhythmic posterior body wall muscle contractions. DEC-7 is highly expressed in the intestinal epithelia and localizes to the cell-cell junction. The increase in rhythmic activity caused by the loss of dec-7 is dependent on the innexin gap junction protein INX-16. Moreover, DEC-7 is required for the clustering of INX-16 to the cell-cell junction of the intestinal epithelia. We hypothesize that DEC-7/SUSD2 regulates INX-16 activity to mediate the rhythmic frequency of the defecation motor program. Thus, our data indicate a critical role of a phylogenetically conserved cell-cell junction protein in mediating an ultradian rhythm in the intestinal epithelia of C. elegans.NEW & NOTEWORTHY The conserved complement group protein DEC-7/SUSD2 acts at the apical cell-cell junction of C. elegans intestinal epithelia to mediate gap junction protein organization and function to facilitate a Ca2+ wave-regulated ultradian behavior.
摘要：
在秀丽隐杆线虫中,有节奏的后体壁肌肉收缩介导了高度规则的排便周期。这些收缩受肠上皮细胞中肌醇1,4,5-三磷酸（InsP3）受体依赖性Ca2振荡的调节。这里,我们发现dec-7中的突变，其编码含有2蛋白（SUSD2）的人Sushi结构域的线虫直系同源物，导致InsP3受体依赖性节律性后体壁肌肉收缩增加。DEC-7在肠上皮细胞中高度表达并且定位于细胞-细胞连接处。由dec-7丢失引起的节律活性增加取决于innexin间隙连接蛋白INX-16。此外，DEC-7是INX-16聚集到肠上皮细胞的细胞-细胞连接处所必需的。我们假设DEC-7/SUSD2调节INX-16活动以调节排便运动程序的节律频率。因此，我们的数据表明，系统发育保守的细胞-细胞连接蛋白在介导秀丽隐杆线虫肠上皮细胞的超节律中起关键作用。
