The Golgi microtubules regulate single cell durotaxis
The Golgi microtubules regulate single cell durotaxis
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DOI：
10.15252/embr.202051094
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发表时间：
2021-02
期刊：
影响因子：
7.7
通讯作者：
Yingxue Rong;Wenzhong Yang;Huiwen Hao;Wenxu Wang;Shao-Zhen Lin;P. Shi;Yuxing Huang;Bo Li
中科院分区：
文献类型：
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作者：
Yingxue Rong;Wenzhong Yang;Huiwen Hao;Wenxu Wang;Shao-Zhen Lin;P. Shi;Yuxing Huang;Bo Li
目前对细胞运动性和方向性的理解在很大程度上依赖于对黏附-肌动蛋白细胞骨架-肌动球蛋白收缩周期的累积研究，而微管在这方面的研究还不够充分。固结性，即细胞沿基质硬度梯度迁移的能力，在发育和疾病中起关键作用。在这里，我们确定了高尔基微管在单细胞重定向迁移中的关键作用。通过对微管加端/焦点粘附相互作用的高通量分析，我们发现这些非中心体微管积极地赋予前沿焦点粘附（FA）动力学。此外，我们设计了一个新的系统，在RGD肽包被的聚丙烯酰胺凝胶中有更高刚度的岛。我们发现，高尔基体的定位是对外部机械信号的响应，高尔基核轴与刚性梯度对齐。总之，我们的工作揭示了单细胞坚硬性的细胞骨架基础。我们提出了一个高尔基核轴作为罗盘和方向盘的模型，通过非中心体微管和FA动力学之间的相互作用来决定细胞的方向性。
Current understandings on cell motility and directionality rely heavily on accumulated investigations of the adhesion–actin cytoskeleton–actomyosin contractility cycles, while microtubules have been understudied in this context. Durotaxis, the ability of cells to migrate up gradients of substrate stiffness, plays a critical part in development and disease. Here, we identify the pivotal role of Golgi microtubules in durotactic migration of single cells. Using high‐throughput analysis of microtubule plus ends/focal adhesion interactions, we uncover that these non‐centrosomal microtubules actively impart leading edge focal adhesion (FA) dynamics. Furthermore, we designed a new system where islands of higher stiffness were patterned within RGD peptide coated polyacrylamide gels. We revealed that the positioning of the Golgi apparatus is responsive to external mechanical cues and that the Golgi–nucleus axis aligns with the stiffness gradient in durotaxis. Together, our work unveils the cytoskeletal underpinning for single cell durotaxis. We propose a model in which the Golgi–nucleus axis serves both as a compass and as a steering wheel for durotactic migration, dictating cell directionality through the interaction between non‐centrosomal microtubules and the FA dynamics.