美国康奈尔大学Jeremy M. Baskin团队近期取得重要工作进展，他们研究提出，磷酸化调控开关可实现依赖细胞周期性蛋白质的重新定位。相关研究成果2024年8月29日在线发表于《自然—细胞生物学》杂志上。

据介绍，用于急性操纵蛋白质定位的工具能够阐明时空定义的功能，但它们对外源触发的依赖可能会干扰细胞生理学。这种局限性在研究有丝分裂时尤为明显，有丝分裂的高度编排事件对扰动很敏感。

研究人员利用衔接蛋白PLEKHA5磷酸化控制、细胞周期依赖性定位变化的偶然发现，开发了一种无需外源刺激的有丝分裂特异性蛋白募集到质膜的系统。

支持有丝分裂的锚定/募集系统包括一个工程化的15 kDa模块，该模块来源于PLEKHA5，能够在有丝分裂过程中通过直接融合或通过GFP-GFP纳米体相互作用将功能性蛋白质货物募集到质膜。支持有丝分裂的锚移/招募系统的应用包括：在有丝分裂过程中侧敲，快速从蛋白质的原生定位中提取蛋白质；有条件地招募脂质代谢酶，对质膜脂质含量进行有丝分裂选择性编辑，而无需外源触发器或扰动性同步方法。

附：英文原文

Title: A phosphorylation-controlled switch confers cell cycle-dependent protein relocalization

Author: Cao, Xiaofu, Huang, Shiying, Wagner, Mateusz M., Cho, Yuan-Ting, Chiu, Din-Chi, Wartchow, Krista M., Lazarian, Artur, McIntire, Laura Beth, Smolka, Marcus B., Baskin, Jeremy M.

Issue&Volume: 2024-08-29

Abstract: Tools for acute manipulation of protein localization enable elucidation of spatiotemporally defined functions, but their reliance on exogenous triggers can interfere with cell physiology. This limitation is particularly apparent for studying mitosis, whose highly choreographed events are sensitive to perturbations. Here we exploit the serendipitous discovery of a phosphorylation-controlled, cell cycle-dependent localization change of the adaptor protein PLEKHA5 to develop a system for mitosis-specific protein recruitment to the plasma membrane that requires no exogenous stimulus. Mitosis-enabled anchor-away/recruiter system comprises an engineered, 15kDa module derived from PLEKHA5 capable of recruiting functional protein cargoes to the plasma membrane during mitosis, either through direct fusion or via GFP–GFP nanobody interaction. Applications of the mitosis-enabled anchor-away/recruiter system include both knock sideways to rapidly extract proteins from their native localizations during mitosis and conditional recruitment of lipid-metabolizing enzymes for mitosis-selective editing of plasma membrane lipid content, without the need for exogenous triggers or perturbative synchronization methods.

DOI: 10.1038/s41556-024-01495-8

Source: https://www.nature.com/articles/s41556-024-01495-8