Chemo-optogenetic Protein Translocation System Using a Photoactivatable Self-Localizing Ligand,ACS Chemical Biology

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Chemo-optogenetic Protein Translocation System Using a Photoactivatable Self-Localizing Ligand
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2021-08-02 , DOI: 10.1021/acschembio.1c00416
Tatsuyuki Yoshii _{1,

2} , Choji Oki ₃ , Rei Watahiki ₄ , Akinobu Nakamura ₁ , Kai Tahara ₃ , Keiko Kuwata ₅ , Toshiaki Furuta ₄ , Shinya Tsukiji _{1,

3}

Affiliation

Manipulating subcellular protein localization using light is a powerful approach for controlling signaling processes with high spatiotemporal precision. The most widely used strategy for this is based on light-induced protein heterodimerization. The use of small synthetic molecules that can control the localization of target proteins in response to light without the need for a second protein has several advantages. However, such methods have not been well established. Herein, we present a chemo-optogenetic approach for controlling protein localization using a photoactivatable self-localizing ligand (paSL). We developed a paSL that can recruit tag-fused proteins of interest from the cytoplasm to the plasma membrane within seconds upon light illumination. This paSL-induced protein translocation (paSLIPT) is reversible and enables the spatiotemporal control of signaling processes in living cells, even in a local region. paSLIPT can also be used to implement simultaneous optical stimulation and multiplexed imaging of molecular processes in a single cell, offering an attractive and novel chemo-optogenetic platform for interrogating and engineering dynamic cellular functions.

中文翻译：

使用光活化自定位配体的化学光遗传学蛋白质易位系统

使用光操纵亚细胞蛋白质定位是一种以高时空精度控制信号传递过程的有效方法。最广泛使用的策略是基于光诱导的蛋白质异二聚化。使用小合成分子可以控制目标蛋白质的定位以响应光而不需要第二种蛋白质有几个优点。然而，这些方法还没有很好地建立。在此，我们提出了一种使用可光活化的自定位配体 (paSL) 控制蛋白质定位的化学光遗传学方法。我们开发了一种 paSL，可以在光照后的几秒钟内将感兴趣的标签融合蛋白从细胞质募集到质膜。这种 paSL 诱导的蛋白质易位 (paSLIPT) 是可逆的，即使在局部区域也能对活细胞中的信号传导过程进行时空控制。paSLIPT 还可用于在单个细胞中实现分子过程的同步光刺激和多路复用成像，为询问和设计动态细胞功能提供有吸引力且新颖的化学光遗传学平台。

更新日期：2021-08-20

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