Coordinate regulation of apical-basal cell polarity and cell-cell adhesion during epithelial development

上皮发育过程中顶底细胞极性和细胞间粘附的协调调节

• 批准号: 200517547
• 负责人: Professor Dr. Andreas Wodarz
• 金额: --
• 依托单位: Institut I für Anatomie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/200517547?language=en
• 关键词: Coordinate; regulation; apical; basal; cell

The formation of the zonula adherens (ZA), an adhesion belt encircling the apical region of the lateral plasma membrane in epithelial cells, is tightly coordinated with the establishment of apical-basal cell polarity. In Drosophila, mutations in genes required for the control of cell polarity, e. g. crumbs (crb), stardust (sdt), bazooka (baz) and aPKC, also affect the formation of the ZA. The formation of spot adherens junctions (AJs), which coalesce to build the contiguous belt of the ZA, requires the function of the homophilic cell-cell adhesion protein DE-cadherin and its binding partners, α- and β-catenin. Spot AJs still form in mutants for the polarity regulators, but their coordinate movement to the apical region of the lateral membrane and their fusion during ZA formation is abolished. Furthermore, the ZA cannot be maintained in epithelia undergoing morphogenetic movements when the function of the polarity regulators is impaired. So far, only limited information is available to understand the crosstalk between the polarity regulators and the proteins of the cadherin-catenin complex, which mediate the adhesion between epithelial cells. In a yeast two-hybrid-screen for interaction partners of Baz, a central regulator of apical-basal polarity in epithelia, we isolated the LIM domain protein encoded by the annotated gene CG31534. CG31534 binds to Baz in vivo and colocalizes precisely with Baz and DE-cadherin at the ZA of ectodermal epi-thelia. CG31534 also binds to and gets phosphorylated by the tyrosine kinase Src42A, which has been implicated in the phosphorylation and regulation of β-catenin. In this project, we will analyze the function of CG31534 and its vertebrate homolog LMO7 with respect to regulation of Src42A activity during ZA formation and junctional remodeling in development.

粘附带(ZA)的形成与顶端-基底细胞极性的建立密切相关。ZA是一条包围上皮细胞侧质膜顶端的粘附带。在果蝇中，控制细胞极性所需的基因突变，如crumbs(CRB)、starust(SDT)、bazooka(Baz)和aPKC，也影响Za的形成。斑点黏附连接(AJs)的形成需要细胞-细胞黏附蛋白DE-Cadherin及其结合伙伴α-和β-Catenin的功能，AJs聚集在一起形成ZA的连续带。在极性调节剂的突变体中，斑点AJ仍然形成，但它们在ZA形成过程中向侧膜顶端的坐标移动和它们的融合被取消。此外，当极性调节器的功能受损时，ZA不能维持在经历形态发生运动的上皮细胞中。到目前为止，只有有限的信息可以用来了解极性调节器和钙粘附素-连环蛋白复合体的蛋白质之间的串扰，它介导了上皮细胞之间的黏附。在酵母双杂交筛选BAZ的相互作用伙伴中，我们分离到了由注释基因CG31534编码的LIM结构域蛋白。CG31534在体内与Baz结合，并与Baz和DE-钙粘附素精确定位于外胚层上皮的Za。CG31534还与酪氨酸激酶Src42a结合并被其磷酸化，该蛋白参与了β-连环蛋白的磷酸化和调节。在这个项目中，我们将分析CG31534及其脊椎动物同源基因LMO7在ZA形成过程中对Src42A活性的调节以及在发育过程中的连接重塑方面的功能。