Lgl/aPKC and Crb regulate the Salvador/Warts/Hippo pathway
Lgl/aPKC and Crb regulate the Salvador/Warts/Hippo pathway
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DOI：
10.4161/fly.4.4.13116
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发表时间：
2010-10-01
期刊：
影响因子：
1.2
通讯作者：
Richardson, Helena E.
中科院分区：
文献类型：
--
作者：
Parsons, Linda M.;Grzeschik, Nicola A.;Richardson, Helena E.
发育生物学的一个关键目标是了解协调器官生长的机制。长期以来，人们已经认识到，控制顶基细胞极性的基因也调节组织生长。细胞极性的丧失如何导致组织的过度生长一直是许多推测的主题。细胞极性调节因子的功能缺失突变是否会导致继发性效应，从而全面解除对细胞增殖的调节，或者这些基因是否专门控制生长途径？最近的三篇论文表明，顶-基底极性决定因子Lgl/aPKC和Crb独立于它们在细胞极性中的作用调节组织生长，并通过萨尔瓦多/疣/河马（SWH）途径协调调节细胞增殖和细胞死亡。Lgl/aPKC是Hippo（Hpo）/Ras相关因子（RASSF）正确定位所需的，而Crb调节Expanded（Ex）的水平和定位，这表明细胞极性决定因素通过不同的机制改变SWH途径活性。在这里，我们回顾了支持这些结论的关键数据，突出剩余的问题，并推测细胞极性复合物与SWH通路相互作用的潜在机制。了解细胞极性调节因子和SWH通路之间的相互作用将提高我们对上皮组织和组织生长在发育过程中如何协调以及在疾病状态（如癌症）中如何受到干扰的认识。
A key goal of developmental biology is to understand the mechanisms that coordinate organ growth. It has long been recognized that the genes that control apico-basal cell polarity also regulate tissue growth. How loss of cell polarity contributes to tissue overgrowth has been the subject of much speculation. Do loss-of-function mutations in cell polarity regulators result in secondary effects that globally deregulate cell proliferation, or do these genes specifically control growth pathways? Three recent papers have shown that the apico-basal polarity determinants Lgl/aPKC and Crb regulate tissue growth independently of their roles in cell polarity and coordinately regulate cell proliferation and cell death via the Salvador/Warts/Hippo (SWH) pathway. Lgl/aPKC are required for the correct localization of Hippo (Hpo)/Ras associated factor (RASSF), while Crb regulates the levels and localization of Expanded (Ex), indicating that cell polarity determinants modify SWH pathway activity by distinct mechanisms. Here, we review the key data that support these conclusions, highlight remaining questions and speculate on the underlying mechanisms by which the cell polarity complexes interact with the SWH pathway. Understanding the interactions between cell polarity regulators and the SWH pathway will improve our knowledge of how epithelial organization and tissue growth are coordinated during development and perturbed in disease states such as cancer.