RanBP1 plays an essential role in directed migration of neural crest cells during development
RanBP1 plays an essential role in directed migration of neural crest cells during development
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RanBP1 在神经嵴细胞发育过程中的定向迁移中发挥重要作用
DOI：
10.1101/2022.05.05.490747
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Barriga E
中科院分区：
文献类型：
--
作者：
Barriga E
集体细胞迁移对于胚胎发育、组织再生和修复是必不可少的，并且与病理状况如癌症转移有关。它在一定程度上是由促进单个细胞中从前到后极性的外部线索指导的。然而，我们对支持细胞响应外部线索的定向运动的途径的理解仍然不完整。为了研究这个问题，我们利用了神经嵴细胞（NC），它们在发育过程中作为集体迁移，以产生包括骨骼和软骨在内的重要结构。使用候选方法，我们发现Ran结合蛋白1（RanBP 1）（核质转运途径的关键效应子）在实现这些细胞的定向迁移方面发挥着重要作用。我们的研究结果表明，RanBP 1是建立前后极性所必需的，因此NC能够进行化学征税。此外，我们的工作表明，RanBP 1在趋化性中的功能涉及极性激酶LKB 1/PAR 4。我们设想，通过Ran/RanBP 1的LKB 1的受管制的核出口是建立前后极性和趋化性所需的关键监管步骤，在NC集体迁移。
Collective cell migration is essential for embryonic development, tissue regeneration and repair, and has been implicated in pathological conditions such as cancer metastasis. It is, in part, directed by external cues that promote front-to-rear polarity in individual cells. However, our understanding of the pathways that underpin the directional movement of cells in response to external cues remains incomplete. To examine this issue we made use of neural crest cells (NC), which migrate as a collective during development to generate vital structures including bones and cartilage. Using a candidate approach, we found an essential role for Ran-binding protein 1 (RanBP1), a key effector of the nucleocytoplasmic transport pathway, in enabling directed migration of these cells. Our results indicate that RanBP1 is required for establishing front-to-rear polarity, so that NCs are able to chemotax. Moreover, our work suggests that RanBP1 function in chemotaxis involves the polarity kinase LKB1/PAR4. We envisage that regulated nuclear export of LKB1 through Ran/RanBP1 is a key regulatory step required for establishing front-to-rear polarity and thus chemotaxis, during NC collective migration.
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