MRC Cell Biology Unit, MRC Laboratory for Molecular Cell Biology and Department of Neuroscience, Physiology and Pharmacology, University College, London, United Kingdom.
PLoS One. 2011 Feb 28;6(2):e17265. doi: 10.1371/journal.pone.0017265.
The Rho family of small GTPases are essential during early embryonic development making it difficult to study their functions in adult animals. Using inducible transgenes expressing either a constitutively active version of the single C. elegans Rho ortholog, RHO-1, or an inhibitor of endogenous Rho (C3 transferase), we demonstrate multiple defects caused by altering Rho signaling in adult C. elegans. Changes in RHO-1 signaling in cholinergic neurons affected locomotion, pharyngeal pumping and fecundity. Changes in RHO-1 signaling outside the cholinergic neurons resulted in defective defecation, ovulation, and changes in C. elegans body morphology. Finally both increased and decreased RHO-1 signaling in adults resulted in death within hours. The multiple post-developmental roles for Rho in C. elegans demonstrate that RhoA signaling pathways continue to be used post-developmentally and the resulting phenotypes provide an opportunity to further study post-developmental Rho signaling pathways using genetic screens.
Rho 家族的小 GTPases 在早期胚胎发育中至关重要，这使得研究它们在成年动物中的功能变得困难。我们使用诱导型转基因表达线虫中单一 Rho 直系同源物 RHO-1 的组成性激活形式或内源性 Rho 的抑制剂（C3 转移酶），证明了改变成年线虫中 Rho 信号会导致多种缺陷。改变胆碱能神经元中的 RHO-1 信号会影响运动、咽泵和生殖力。在胆碱能神经元外改变 RHO-1 信号会导致排便、排卵和线虫体形态的缺陷。最后，成年线虫中 RHO-1 信号的增加和减少都会导致数小时内死亡。Rho 在秀丽隐杆线虫中的多种发育后作用表明，RhoA 信号通路在发育后仍在继续使用，由此产生的表型为使用遗传筛选进一步研究发育后 Rho 信号通路提供了机会。
