Guidance receptor promotes the asymmetric distribution of exocyst and recycling endosome during collective cell migration
Guidance receptor promotes the asymmetric distribution of exocyst and recycling endosome during collective cell migration
复制标题
引导受体在集体细胞迁移过程中促进外囊和回收内体的不对称分布
DOI：
10.1242/dev.094979
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发表时间：
2013-12-01
期刊：
影响因子：
4.6
通讯作者：
Chen, Jiong
中科院分区：
文献类型：
--
作者：
Wan, Ping;Wang, Dou;Chen, Jiong
在集体迁移过程中，引导受体向下游发出信号，导致分子的极化分布，包括细胞骨架调节剂和引导受体本身，以响应趋化因子的细胞外梯度。然而，在一组细胞迁移的背景下，不对称性产生的潜在机制还没有得到很好的理解。以果蝇卵巢边缘细胞为模型系统，研究发现，受体酪氨酸激酶（RTK）PDGF/VEGF受体（PVR）参与了边缘细胞群中主导细胞内体和外囊的极化分布。有趣的是，PVR信号通过小GTCRac积极影响Rab 11标记的再循环内体的水平，可能是在F-肌动蛋白依赖的方式。相反，外囊复合物组分Sec 3是RTK活性和F-肌动蛋白的不对称定位所需的，类似于先前报道的Rab 11的功能。总而言之，这些结果表明边缘细胞中存在正反馈循环，其中PVR等RTK的作用是诱导领先细胞中更高水平的囊泡回收和束缚活性，这反过来又使RTK活性以更加极化的方式分布在前方。我们还提供了证据表明，E-cadherin，边缘细胞迁移的主要粘附分子，是Rab 11标记的再循环内体中的特定货物，Sec 3是将含E-cadherin的囊泡递送到膜所需的。
During collective migration, guidance receptors signal downstream to result in a polarized distribution of molecules, including cytoskeletal regulators and guidance receptors themselves, in response to an extracellular gradient of chemotactic factors. However, the underlying mechanism of asymmetry generation in the context of the migration of a group of cells is not well understood. Using border cells in the Drosophila ovary as a model system for collective migration, we found that the receptor tyrosine kinase (RTK) PDGF/VEGF receptor (PVR) is required for a polarized distribution of recycling endosome and exocyst in the leading cells of the border cell cluster. Interestingly, PVR signaled through the small GTPase Rac to positively affect the levels of Rab11-labeled recycling endosomes, probably in an F-actin-dependent manner. Conversely, the exocyst complex component Sec3 was required for the asymmetric localization of RTK activity and F-actin, similar to that previously reported for the function of Rab11. Together, these results suggested a positive-feedback loop in border cells, in which RTKs such as PVR act to induce a higher level of vesicle recycling and tethering activity in the leading cells, which in turn enables RTK activity to be distributed in a more polarized fashion at the front. We also provided evidence that E-cadherin, the major adhesion molecule for border cell migration, is a specific cargo in the Rab11-labeled recycling endosomes and that Sec3 is required for the delivery of the E-cadherin-containing vesicles to the membrane.