The role of the cytoskeleton in regulating contractile tubes, using the c. Elegans spermatheca as an In vivo model

Contractile tubes are a hallmark of many animal organs. Misregulation of contractility is responsible for several human diseases, such as hypertension and asthma. Our in vivo model for a contractile tube is the C. elegans spermatheca, which is part of the nematode reproductive system, where fertilization takes place. Spermathecal cells exhibit features of smooth muscle cells and the entire tissue is readily accessible to genetic manipulation and live imaging. Misregulation of spermathecal contractility has deleterious consequences for fertility. Previous work has shown that activity of the small GTPase RHO-1 is essential for spermathecal contraction. However, the molecular mechanisms controlling the spatiotemporal activation of RHO-1 are still poorly understood. Here, we performed an RNAi knockdown screen for the known RhoGEFs in C. elegans, and found that RHGF-1 regulates RHO-1 activity in the spermatheca. Using genome editing to fluorescently tag RHGF-1 and performing live imaging on a confocal microscope, we discovered that RHGF-1 re-localizes from the cytoplasm to actomyosin stress fibers during ovulation. We hypothesize that mechanical stretching of the spermatheca by an ovulating oocyte serves as a trigger to initiate the biochemical signaling ultimately leading to contraction. This knowledge may help design future strategies for the treatment of human diseases caused by misregulation of tubular contractility.