美国宾夕法尼亚大学Lukasz J. Bugaj小组发现，一种温度诱导的蛋白质模块可用于控制哺乳动物细胞命运。相关论文于2025年1月23日在线发表在《自然—方法学》杂志上。

研究人员介绍了一种可以通过小幅度温度变化可逆切换的蛋白质，这种刺激既具有穿透性又是动态的。该蛋白质名为Melt（温度诱导的膜定位），在温度降低时会聚合并转位到质膜上。研究人员生成了一个Melt变体库，其切换温度范围从30°C到40°C，包括两个在37°C及以上操作的变体。

Melt是一个高度模块化的细胞功能执行器，允许对多种过程进行热控，包括信号传导、蛋白水解、核转运、细胞骨架重组和细胞死亡。最后，Melt在小鼠人类癌症模型中允许对细胞死亡进行热控。

Melt代表了一种多功能的热遗传模块，可用于简便、无创且时空定义明确的哺乳动物细胞控制，具有广泛的生物技术和生物医学潜力。

据了解，可诱导的蛋白质开关目前在组织和生物体中的应用受到限制，因为常见的诱导因子无法在光学密集的环境中精确地控制空间和时间。

附：英文原文

Title: A temperature-inducible protein module for control of mammalian cell fate

Author: Benman, William, Huang, Zikang, Iyengar, Pavan, Wilde, Delaney, Mumford, Thomas R., Bugaj, Lukasz J.

Issue&Volume: 2025-01-23

Abstract: Inducible protein switches are currently limited for use in tissues and organisms because common inducers cannot be controlled with precision in space and time in optically dense settings. Here, we introduce a protein that can be reversibly toggled with a small change in temperature, a stimulus that is both penetrant and dynamic. This protein, called Melt (Membrane localization using temperature) oligomerizes and translocates to the plasma membrane when temperature is lowered. We generated a library of Melt variants with switching temperatures ranging from 30°C to 40°C, including two that operate at and above 37°C. Melt was a highly modular actuator of cell function, permitting thermal control over diverse processes including signaling, proteolysis, nuclear shuttling, cytoskeletal rearrangements and cell death. Finally, Melt permitted thermal control of cell death in a mouse model of human cancer. Melt represents a versatile thermogenetic module for straightforward, non-invasive and spatiotemporally defined control of mammalian cells with broad potential for biotechnology and biomedicine.

DOI: 10.1038/s41592-024-02572-4

Source: https://www.nature.com/articles/s41592-024-02572-4