Drosophila Cip4 and WASp Define a Branch of the Cdc42-Par6-aPKC Pathway Regulating E-Cadherin Endocytosis
Drosophila Cip4 and WASp Define a Branch of the Cdc42-Par6-aPKC Pathway Regulating E-Cadherin Endocytosis
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DOI：
10.1016/j.cub.2008.09.063
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发表时间：
2008-11-11
期刊：
影响因子：
9.2
通讯作者：
Bellaiche, Yohanns
中科院分区：
文献类型：
--
作者：
Leibfried, Andrea;Fricke, Robert;Bellaiche, Yohanns
背景：上皮的功能和形态不可或缺的是细胞-细胞连接的网格，称为粘附连接（AJs）。AJ的稳定性和可塑性依赖于E-钙粘蛋白的胞吐和胞吞作用。调节E-钙粘蛋白（E-Cad）胞吐的AJs的机制有牵连的外囊复合物的蛋白质，但调节E-Cad内吞的AJs的机制仍然不太好理解。结果：在这里，我们表明，Cdc 42，Par 6，或aPKC功能丧失是伴随着顶端E-Cad细胞内点状结构的积累和破坏AJs在果蝇上皮细胞。这些点状结构来自于从AJs发出的大而畸形的内吞囊泡;在阻断发动蛋白突变细胞中的囊泡断裂时也观察到的表型。我们证明，果蝇Cdc 42相互作用蛋白4（Cip 4）是一个Cdc 42效应器，与果蝇中的发动蛋白和Arp 2/3激活剂WASp相互作用。因此，Cip 4，WASp，或Arp 2/3的功能丧失也导致缺陷的E-Cadherin endocytosis.Conclusion：总之，我们的研究结果表明，Cdc 42的功能与Par 6和aPKC调节E-Cad内吞作用和定义Cip 4和WASp作为监管机构的早期E-Cad内吞事件在上皮组织。
Background: Integral to the function and morphology of the epithelium is the lattice of cell-cell junctions known as adherens junctions (AJs). AJ stability and plasticity relies on E-Cadherin exocytosis and endocytosis. A mechanism regulating E-Cadherin (E-Cad) exocytosis to the AJs has implicated proteins of the exocyst complex, but mechanisms regulating E-Cad endocytosis from the AJs remain less well understood.Results: Here we show that Cdc42, Par6, or aPKC loss of function is accompanied by the accumulation of apical E-Cad intracellular punctate structures and the disruption of AJs in Drosophila epithelial cells. These punctate structures derive from large and malformed endocytic vesicles that emanate from the AJs; a phenotype that is also observed upon blocking vesicle scission in dynamin mutant cells. We demonstrate that the Drosophila Cdc42-interacting protein 4 (Cip4) is a Cdc42 effector that interacts with Dynamin and the Arp2/3 activator WASp in Drosophila. Accordingly, Cip4, WASp, or Arp2/3 loss of function also results in defective E-Cadherin endocytosis.Conclusion: Altogether our results show that Cdc42 functions with Par6 and aPKC to regulate E-Cad endocytosis and define Cip4 and WASp as regulators of the early E-Cad endocytic events in epithelial tissue.