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非遗传工程策略调控活细胞中受体寡聚化。

Nongenetic engineering strategies for regulating receptor oligomerization in living cells.

机构信息

MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, People's Republic of China.

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

出版信息

Chem Soc Rev. 2020 Mar 9;49(5):1545-1568. doi: 10.1039/c9cs00473d.

DOI:10.1039/c9cs00473d
PMID:32040109
Abstract

Cell surface receptors are important proteins that mediate communication between the cells and their outside environment, and also play essential roles in the control of a wide variety of biological processes, such as cell cycle, proliferation, communication, migration and apoptosis. Receptor oligomerization is an essential signal transduction mechanism that cell surface receptors use to transmit extracellular signals into the internal cytosol cellular machinery. Therefore, regulating receptor oligomerization provides an opportunity to customize cellular signaling and to direct cellular behavior in a user-defined manner. Some techniques have been developed for receptor oligomerization regulation, such as chemically induced dimerization (CID) and optogenetics, which involve traditional genetic engineering. However, the process of genetic manipulation is time-consuming, unpredictable and inefficient. Thus, development of nongenetic strategies for precisely regulating receptor oligomerization remains a desirable goal. Recently, along with the utilization of DNA, protein, small molecules and stimuli-responsive materials-based nongenetic engineering strategies, various receptor oligomerization and multiple cellular behaviors could be regulated, including migration, proliferation, apoptosis, differentiation and immune responses, etc. In this review, we aim to systematically introduce advances in the development of nongenetic engineering strategies for regulating receptor oligomerization, and provide insights into the existing challenges and future perspectives of this field.

摘要

细胞表面受体是一种重要的蛋白质,它们介导细胞与其外部环境之间的通讯,并且在控制多种生物过程中起着至关重要的作用,如细胞周期、增殖、通讯、迁移和凋亡。受体寡聚化是细胞表面受体用来将细胞外信号传递到细胞内部细胞质机器的一种基本信号转导机制。因此,调节受体寡聚化提供了一种机会,可以定制细胞信号,并以用户定义的方式指导细胞行为。已经开发了一些用于受体寡聚化调节的技术,例如化学诱导二聚体(CID)和光遗传学,它们涉及传统的基因工程。然而,遗传操作的过程既耗时又不可预测,效率也不高。因此,开发精确调节受体寡聚化的非遗传策略仍然是一个理想的目标。最近,随着 DNA、蛋白质、小分子和刺激响应材料的非遗传工程策略的应用,各种受体寡聚化和多种细胞行为都可以得到调节,包括迁移、增殖、凋亡、分化和免疫反应等。在这篇综述中,我们旨在系统地介绍用于调节受体寡聚化的非遗传工程策略的最新进展,并提供对该领域现有挑战和未来展望的见解。

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