Understanding the role of the ESCRT-associated protein MITD1 in linking cytoskeleton and membrane remodelling

了解 ESCRT 相关蛋白 MITD1 在连接细胞骨架和膜重塑中的作用

• 批准号: BB/N000501/1
• 负责人: Monica Agromayor
• 金额: $ 46.23万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN000501%2F1
• 关键词: Understanding; role; ESCRT; associated; protein

The cortical cytoskeleton or cell cortex is a thin network of actin, myosin and associated proteins that lies beneath the plasma membrane in most eukaryotic cells. The way in which the cell cortex and the plasma membrane interact with each other changes in response to the environment and controls fundamental cellular processes including cell proliferation and motility. Thus, understanding in detail the molecular mechanisms that regulate the cross talk between the actin cytoskeleton and the plasma membrane is of considerable importance both in health and disease. We have recently identified the human protein, microtubule interacting and transport domain containing 1 (MITD1), as an important component of the cellular machinery that orchestrates the cytoskeleton and membrane reorganization needed to bring about cytokinetic abscission, the last step of cell division. Furthermore, our preliminary data suggest that MITD1 is part of a network of proteins that participate in several processes with a similar requirement to coordinate actin dynamics and membrane remodelling events including membrane repair and cell division. The aim of this project is to understand further how MITD1 participates in these processes. The results of this research could provide the foundation for new strategies for targeting cancer cells and rare genetic diseases.

皮质细胞骨架或细胞皮质是肌动蛋白、肌球蛋白和相关蛋白质的薄网络，位于大多数真核细胞的质膜之下。细胞皮层和质膜相互作用的方式响应于环境而改变，并控制基本的细胞过程，包括细胞增殖和运动。因此，详细了解调节肌动蛋白细胞骨架和质膜之间的串扰的分子机制在健康和疾病中都是相当重要的。我们最近已经确定了人类蛋白质，微管相互作用和运输结构域包含1（MITD1），作为一个重要组成部分的细胞机器，协调细胞骨架和膜重组需要带来细胞动力学的分裂，细胞分裂的最后一步。此外，我们的初步数据表明，MITD1是参与几个过程的蛋白质网络的一部分，这些过程具有类似的要求，以协调肌动蛋白动力学和膜重塑事件，包括膜修复和细胞分裂。本项目的目的是进一步了解MITD1如何参与这些过程。这项研究的结果可以为靶向癌细胞和罕见遗传疾病的新策略提供基础。

项目成果

The ESCRT machinery counteracts Nesprin-2G-mediated mechanical forces during nuclear envelope repair.

• DOI: 10.1016/j.devcel.2021.10.022
• 发表时间: 2021-12-06
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: Wallis SS;Ventimiglia LN;Otigbah E;Infante E;Cuesta-Geijo MA;Kidiyoor GR;Carbajal MA;Fleck RA;Foiani M;Garcia-Manyes S;Martin-Serrano J;Agromayor M
• 通讯作者: Agromayor M

Biochemical characterisation of UMAD1 and functional implications for ESCRT mediated cytokinetic abscission

UMAD1 的生化特征及其对 ESCRT 介导的细胞分裂脱落的功能影响

• 发表时间: 2020
• 作者: Scourfield Edward

The role of the ESCRT-associated protein BROX at the nuclear envelope

ESCRT 相关蛋白 BROX 在核膜中的作用

• 发表时间: 2021
• 作者: Samuel Stephen Wallis