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利用工程化肌球蛋白马达对细胞通讯进行光遗传学操控。

Optogenetic manipulation of cellular communication using engineered myosin motors.

机构信息

Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA.

Department of Developmental Biology, Stanford University, Stanford, CA, USA.

出版信息

Nat Cell Biol. 2021 Feb;23(2):198-208. doi: 10.1038/s41556-020-00625-2. Epub 2021 Feb 1.

DOI:10.1038/s41556-020-00625-2
PMID:33526902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7880895/
Abstract

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.

摘要

细胞通过诸如神经突和丝状伪足等细胞突起实现高效和精确的通讯，但缺乏能够选择性地操纵其组成和动力学的基因编码工具。在这里，我们提出了一种多功能的光遗传学工具盒，其中包含人工多头肌球蛋白马达，可在长细胞延伸内双向移动，并允许用光选择性地运输 GFP 标记的货物。利用这些工程化的马达，我们可以运输大的跨膜受体和细胞器以及肌动蛋白重塑因子，以控制丝状伪足和神经突的动力学。使用优化的体内成像方案，我们进一步证明，在蝾螈肢体截肢后，会形成复杂的丝状伪足延伸阵列。我们选择性地调节这些丝状伪足延伸，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，这个工具包有可能以前所未有的精度来操纵细胞通讯。

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