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

粘附带（zonula adherens， ZA）的形成与细胞顶基极性的建立密切相关，ZA是上皮细胞侧质膜顶端区域的粘附带。在果蝇中，控制细胞极性所需的基因突变，如crumb （crb）、stardust （sdt）、bazooka （baz）和aPKC，也会影响ZA的形成。斑点粘附连接（spot adhesion junction, AJs）的形成需要同源性细胞-细胞粘附蛋白DE-cadherin及其结合伙伴α-和β-catenin的作用。极性调节因子在突变体中仍然形成斑点AJs，但它们向外侧膜顶端区域的坐标运动和ZA形成过程中的融合被取消。此外，当极性调节因子的功能受损时，ZA不能在发生形态发生运动的上皮中维持。到目前为止，关于极性调节因子与钙粘蛋白-连环蛋白复合物之间的串扰的信息有限，钙粘蛋白复合物介导上皮细胞之间的粘附。在酵母双杂交筛选中，我们分离出了由注释基因CG31534编码的LIM结构域蛋白。CG31534在体内与Baz结合，并在外胚层上皮ZA处与Baz和DE-cadherin精确地共定位。CG31534还与酪氨酸激酶Src42A结合并被其磷酸化，这与β-catenin的磷酸化和调控有关。在本项目中，我们将分析CG31534及其脊椎动物同源物LMO7在ZA形成和发育中连接重塑过程中调控Src42A活性的功能。

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.