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发现一种作为荧光探针和功能探针支架的F-肌动蛋白结合小分子。

Discovery of an F-actin-binding small molecule serving as a fluorescent probe and a scaffold for functional probes.

作者信息

Takagi Takeru, Ueno Tasuku, Ikawa Keisuke, Asanuma Daisuke, Nomura Yusuke, Uno Shin-Nosuke, Komatsu Toru, Kamiya Mako, Hanaoka Kenjiro, Okimura Chika, Iwadate Yoshiaki, Hirose Kenzo, Nagano Tetsuo, Sugimura Kaoru, Urano Yasuteru

机构信息

Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Yayoi 2-11-16, Bunkyo-ku, Tokyo 113-0032, Japan.

出版信息

Sci Adv. 2021 Nov 19;7(47):eabg8585. doi: 10.1126/sciadv.abg8585.

DOI:10.1126/sciadv.abg8585
PMID:34797716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8604405/
Abstract

Actin is a ubiquitous cytoskeletal protein, forming a dynamic network that generates mechanical forces in the cell. There is a growing demand for practical and accessible tools for dissecting the role of the actin cytoskeleton in cellular function, and the discovery of a new actin-binding small molecule is an important advance in the field, offering the opportunity to design and synthesize of new class of functional molecules. Here, we found an F-actin–binding small molecule and introduced two powerful tools based on a new class of actin-binding small molecule: One enables visualization of the actin cytoskeleton, including super-resolution imaging, and the other enables highly specific green light–controlled fragmentation of actin filaments, affording unprecedented control of the actin cytoskeleton and its force network in living cells.

摘要

肌动蛋白是一种普遍存在的细胞骨架蛋白,形成一个动态网络,在细胞中产生机械力。对于剖析肌动蛋白细胞骨架在细胞功能中的作用而言,实用且易于获取的工具需求日益增长,而一种新的肌动蛋白结合小分子的发现是该领域的一项重要进展,为设计和合成新型功能分子提供了契机。在此,我们发现了一种F-肌动蛋白结合小分子,并基于一类新型肌动蛋白结合小分子引入了两种强大的工具:一种能够实现肌动蛋白细胞骨架的可视化,包括超分辨率成像,另一种能够实现肌动蛋白丝的高度特异性绿光控制断裂,从而在活细胞中对肌动蛋白细胞骨架及其力网络实现前所未有的控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/c69c3a2c8fff/sciadv.abg8585-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/b53dac776367/sciadv.abg8585-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/8ce5eefed64f/sciadv.abg8585-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/061bd8b5fd39/sciadv.abg8585-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/c69c3a2c8fff/sciadv.abg8585-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/b53dac776367/sciadv.abg8585-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/8ce5eefed64f/sciadv.abg8585-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/061bd8b5fd39/sciadv.abg8585-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5a7/8604405/c69c3a2c8fff/sciadv.abg8585-f4.jpg

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