IRCM, Inserm, University of Montpellier, ICM, Montpellier, France.
IRCM, Inserm, University of Montpellier, ICM, Montpellier, France
J Cell Biol. 2018 Mar 5;217(3):1047-1062. doi: 10.1083/jcb.201705107. Epub 2018 Jan 11.
During development, cell numbers are tightly regulated, ensuring that tissues and organs reach their correct size and shape. Recent evidence has highlighted the intricate connections between the cytoskeleton and the regulation of the key growth control Hippo pathway. Looking for apical scaffolds regulating tissue growth, we describe that big bang (Bbg), a poorly characterized multi-PDZ scaffold, controls epithelial tissue growth without affecting epithelial polarity and architecture. -mutant tissues are smaller, with fewer cells that are less apically constricted than normal. We show that Bbg binds to and colocalizes tightly with the β-heavy-Spectrin/Kst subunit at the apical cortex and promotes Yki activity, F-actin enrichment, and the phosphorylation of the myosin II regulatory light chain Spaghetti squash. We propose a model in which the spectrin cytoskeleton recruits Bbg to the cortex, where Bbg promotes actomyosin contractility to regulate epithelial tissue growth.
在发育过程中，细胞数量受到严格调控，以确保组织和器官达到正确的大小和形状。最近的证据强调了细胞骨架与关键生长控制 Hippo 途径的调节之间的复杂联系。为了寻找调节组织生长的顶端支架，我们描述了一个功能未知的多 PDZ 支架 big bang (Bbg)，它可以控制上皮组织的生长，而不影响上皮细胞的极性和结构。Bbg 突变的组织更小，细胞数量更少，细胞顶部分布更狭窄。我们发现 Bbg 与β-重链 spectrin/Kst 亚基结合，并在上皮细胞顶端皮层紧密共定位，促进 Yki 活性、F-肌动蛋白富集以及肌球蛋白 II 调节轻链 Spaghetti squash 的磷酸化。我们提出了一个模型，即 spectrin 细胞骨架将 Bbg 招募到皮层，Bbg 促进肌动球蛋白收缩来调节上皮组织生长。
