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Optogenetic manipulation of cellular communication using engineered myosin motors
Nature Cell Biology ( IF 17.3 ) Pub Date : 2021-02-01 , DOI: 10.1038/s41556-020-00625-2
Zijian Zhang 1, 2, 3 , Nicolas Denans 2, 3, 4 , Yingfei Liu 5, 6, 7 , Olena Zhulyn 2, 3 , Hannah D Rosenblatt 2, 3 , Marius Wernig 5, 6 , Maria Barna 2, 3
Affiliation  

Cells achieve highly efficient and accurate communication through cellular projections such as neurites and filopodia, yet there is a lack of genetically encoded tools that can selectively manipulate their composition and dynamics. Here, we present a versatile optogenetic toolbox of artificial multi-headed myosin motors that can move bidirectionally within long cellular extensions and allow for the selective transport of GFP-tagged cargo with light. Utilizing these engineered motors, we could transport bulky transmembrane receptors and organelles as well as actin remodellers to control the dynamics of both filopodia and neurites. Using an optimized in vivo imaging scheme, we further demonstrate that, upon limb amputation in axolotls, a complex array of filopodial extensions is formed. We selectively modulated these filopodial extensions and showed that they re-establish a Sonic Hedgehog signalling gradient during regeneration. Considering the ubiquitous existence of actin-based extensions, this toolbox shows the potential to manipulate cellular communication with unprecedented accuracy.



中文翻译:

使用工程肌球蛋白马达进行细胞通讯的光遗传学操作

细胞通过神经突和丝状伪足等细胞投射实现高效、准确的通讯,但缺乏可以选择性操纵其组成和动态的基因编码工具。在这里,我们提出了一种人工多头肌球蛋白马达的多功能光遗传学工具箱,它可以在长细胞延伸内双向移动,并允许用光选择性运输 GFP 标记的货物。利用这些工程马达,我们可以运输庞大的跨膜受体和细胞器以及肌动蛋白重塑剂来控制丝状伪足和神经突的动态。使用优化的体内成像方案,我们进一步证明,在蝾螈截肢后,会形成复杂的丝状足延伸阵列。我们选择性地调节这些丝状足延伸,并表明它们在再生过程中重新建立了 Sonic Hedgehog 信号梯度。考虑到基于肌动蛋白的延伸的普遍存在,该工具箱显示了以前所未有的准确性操纵细胞通信的潜力。

更新日期:2021-02-01
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