Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, New York, United States.
Department of Biology, Skidmore College, Saratoga Springs, New York, United States.
Am J Physiol Cell Physiol. 2023 May 1;324(5):C1158-C1170. doi: 10.1152/ajpcell.00552.2022. Epub 2023 Apr 17.
In , 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 Ca oscillations in intestinal epithelial cells. Here, we find that mutations in , 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 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 . The conserved complement group protein DEC-7/SUSD2 acts at the apical cell-cell junction of intestinal epithelia to mediate gap junction protein organization and function to facilitate a Ca2+ wave-regulated ultradian behavior.
在秀丽隐杆线虫中,有节奏的体壁后肌肉收缩介导高度规律的排粪周期。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 Ca 振荡调节。在这里,我们发现编码人类 Sushi 结构域包含蛋白 2(SUSD2)线虫同源物的 的突变导致 InsP3 受体依赖性有节奏的体壁后肌肉收缩增加。DEC-7 在肠上皮细胞中高度表达,并定位于细胞-细胞连接。缺失 引起的节律性活性增加依赖于连接蛋白间隙连接蛋白 INX-16。此外,DEC-7 是 INX-16 聚集到肠上皮细胞-细胞连接所必需的。我们假设 DEC-7/SUSD2 调节 INX-16 活性以介导排粪运动程序的节律频率。因此,我们的数据表明,一个进化上保守的细胞-细胞连接蛋白在介导肠上皮细胞的超高频节律中起着关键作用。保守的补体组蛋白 DEC-7/SUSD2 作用于 肠上皮细胞的顶端细胞-细胞连接,调节间隙连接蛋白的组织和功能,以促进 Ca2+波调节的超高频行为。