Epithelial tubules, consisting of the epithelial cell sheet with a central lumen, are the basic structure of many organs. Mechanical forces play an important role in epithelial tubulogenesis; however, little is known about the mechanisms controlling the mechanical forces during epithelial tubule morphogenesis. Solo (also known as ARHGEF40) is a RhoA-targeting guanine-nucleotide exchange factor that is involved in mechanical force-induced RhoA activation and stress fiber formation. Solo binds to keratin-8/keratin-18 (K8/K18) filaments, and this interaction plays a crucial role in mechanotransduction. In this study, we examined the roles of Solo and K8/K18 filaments in epithelial tubulogenesis using MDCK cells cultured in 3D collagen gels. Knockdown of either Solo or K18 resulted in rounder tubules with increased lumen size, indicating that Solo and K8/K18 filaments play critical roles in forming the elongated morphology of epithelial tubules. Moreover, knockdown of Solo or K18 decreased the level of diphosphorylated myosin light chain (a marker of contractile force) at the luminal and outer surfaces of tubules, suggesting that Solo and K8/K18 filaments are involved in the generation of the myosin II-mediated contractile force during epithelial tubule morphogenesis. In addition, K18 filaments were normally oriented along the long axis of the tubule, but knockdown of Solo perturbed their orientation. These results suggest that Solo plays crucial roles in forming the elongated morphology of epithelial tubules and in regulating myosin II activity and K18 filament organization during epithelial tubule formation.Key words: epithelial tubulogenesis, Solo, keratin, Rho-GEF, myosin.

中文翻译：

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独奏和角蛋白长丝调节上皮小管的形态。

上皮小管由上皮细胞片和中心管腔组成，是许多器官的基本结构。机械力在上皮小管生成中起重要作用。然而，关于上皮小管形态发生过程中控制机械力的机制知之甚少。Solo（也称为ARHGEF40）是一种靶向RhoA的鸟嘌呤核苷酸交换因子，参与机械力诱导的RhoA活化和应力纤维形成。Solo与角蛋白8 /角蛋白18（K8 / K18）细丝结合，这种相互作用在机械转导中起关键作用。在这项研究中，我们使用在3D胶原蛋白凝胶中培养的MDCK细胞，检查了Solo和K8 / K18细丝在上皮小管生成中的作用。击倒Solo或K18会导致管腔尺寸增大的圆形小管，表明Solo和K8 / K18细丝在形成上皮小管的伸长形态中起关键作用。此外，Solo或K18的敲低降低了小管腔和外表面的二磷酸肌球蛋白轻链（收缩力的标记）的水平，这表明Solo和K8 / K18细丝参与了肌球蛋白II介导的生成。上皮小管形态发生过程中的收缩力。此外，K18细丝通常沿小管的长轴定向，但Solo的敲低干扰了它们的定向。这些结果表明Solo在上皮小管形成过程中起着伸长的上皮小管形态，调节肌球蛋白II活性和K18细丝组织的作用。关键词：上皮小管形成，Solo，角蛋白，Rho-GEF，