Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila
Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila
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DOI：
10.1242/dev.00361
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发表时间：
2003-04-01
期刊：
影响因子：
4.6
通讯作者：
Hayashi, S
中科院分区：
文献类型：
--
作者：
Chihara, T;Kato, K;Hayashi, S
细胞重排，伴随着钙粘蛋白介导的细胞粘附的快速组装和拆卸，在上皮形态发生中起着至关重要的作用。各种体外和细胞培养的研究表明，小GTd-Rae是细胞粘附的关键调节因子，但这一概念需要在胚胎发育的背景下进行验证。我们利用果蝇的气管系统来研究Rae在上皮细胞重排中的功能，特别关注其在调节上皮钙粘蛋白活性中的作用。我们发现，减少Rae活性导致细胞连接在胚胎表皮和气管上皮细胞，这是伴随着增加果蝇E-钙粘蛋白-连环蛋白复合物的量的转录后机制的扩展。降低Rac活性抑制动态上皮细胞重排。另一方面，Rae的过度活化抑制新合成的E-钙粘蛋白组装成细胞连接，并引起气管细胞粘附的丧失，导致细胞从上皮细胞脱离。因此，在果蝇气管发育的背景下，Rae活性必须保持在平衡细胞连接处E-钙粘蛋白组装和拆卸所需的水平。与其在细胞运动中的作用一起，Rae调节细胞粘附的可塑性，从而确保上皮层顺利重塑为小管。
Cell rearrangement, accompanied by the rapid assembly and disassembly of cadherin-mediated cell adhesions, plays essential roles in epithelial morphogenesis. Various in vitro and cell culture studies on the small GTPase Rae have suggested it to be a key regulator of cell adhesion, but this notion needs to be verified in the context of embryonic development. We used the tracheal system of Drosophila to investigate the function of Rae in the epithelial cell rearrangement, with a special attention to its role in regulating epithelial cadherin activity. We found that a reduced Rae activity led to an expansion of cell junctions in the embryonic epidermis and tracheal epithelia, which was accompanied by an increase in the amount of Drosophila E-Cadherin-Catenin complexes by a post-transcriptional mechanism. Reduced Rac activity inhibited dynamic epithelial cell rearrangement. Hyperactivation of Rae, on the other hand, inhibited assembly of newly synthesized E-Cadherin into cell junctions and caused loss of tracheal cell adhesion, resulting in cell detachment from the epithelia. Thus, in the context of Drosophila tracheal development, Rae activity must be maintained at a level necessary to balance the assembly and disassembly of E-Cadherin at cell junctions. Together with its role in cell motility, Rae regulates plasticity of cell adhesion and thus ensures smooth remodeling of epithelial sheets into tubules.