Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, New York.
Department of Clinical Laboratory Sciences, SUNY Upstate Medical University, Syracuse, New York.
Cytoskeleton (Hoboken). 2019 Apr;76(4):322-336. doi: 10.1002/cm.21547. Epub 2019 Jun 27.
Epithelial cell-cell junctions have dual roles of accommodating morphological changes in an epithelium, while maintaining cohesion during those changes. An abundance of junction proteins has been identified, but many details on how intercellular junctions respond to morphological changes remain unclear. In Caenorhabditis elegans, the spermatheca is an epithelial sac that repeatedly dilates and constricts to allow ovulation. It is thought that the junctions between spermatheca epithelial cells undergo reversible partial unzipping to allow rapid dilation. Previously, we found that EXC-6, a C. elegans protein homolog of the human disease-associated formin INF2, is expressed in the spermatheca and promotes oocyte entry. We show here that EXC-6 localizes toward the apical aspect of the spermatheca epithelial junctions, and that the EXC-6-labeled junction domains "unzip" and dramatically flatten with oocyte entry into the spermatheca. We demonstrate that the C-terminal tail of EXC-6 is necessary and sufficient for junction localization. Moreover, expression of the tail alone worsens ovulation defects, suggesting this region not only mediates EXC-6 localization, but also interacts with other components important for junction remodeling.
上皮细胞-细胞连接具有双重作用,既能适应上皮形态的变化,又能在变化过程中保持细胞间的黏附。已经鉴定出大量的连接蛋白,但细胞连接如何响应形态变化的许多细节仍然不清楚。在秀丽隐杆线虫中,受精囊是一个上皮囊,它反复扩张和收缩以允许排卵。人们认为,受精囊上皮细胞之间的连接经历可逆的部分解拉链,以允许快速扩张。之前,我们发现 EXC-6,线虫与人源疾病相关formin INF2 的蛋白同源物,在受精囊中表达,并促进卵母细胞进入。我们在这里表明,EXC-6 定位于受精囊上皮连接的顶端,并且 EXC-6 标记的连接域“解拉链”并随着卵母细胞进入受精囊而显著变平。我们证明 EXC-6 的 C 末端尾部对于连接定位是必需和充分的。此外,单独表达尾部会加重排卵缺陷,这表明该区域不仅介导 EXC-6 的定位,还与其他对于连接重塑重要的成分相互作用。