Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Naples, Italy.
Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
Traffic. 2019 Oct;20(10):785-802. doi: 10.1111/tra.12682. Epub 2019 Sep 1.
The mammalian Golgi apparatus is organized in the form of a ribbon-like structure positioned near the centrosome. Despite its multimodular organization, the Golgi complex is characterized by a prominent structural plasticity, which is crucial during essential physiological processes, such as the G2 phase of the cell cycle, during which the Golgi ribbon must be "unlinked" into isolated stacks to allow progression into mitosis. Here we show that the Golgi-associated protein GRASP65, which is well known for its role in Golgi stacking and ribbon formation, is also required for the organization of the microtubule cytoskeleton. GRASP65 is not involved in microtubule nucleation or anchoring. Instead, it is required for the stabilization of newly nucleated microtubules, leading to their acetylation and clustering of Golgi stacks. Ribbon formation and microtubule stabilization are both regulated by JNK/ERK-mediated phosphorylation of S274 of GRASP65, suggesting that this protein can coordinate the Golgi structure with microtubule organization. In agreement with an important role, tubulin acetylation is strongly reduced during the G2 phase of the cell cycle, allowing the separation of the Golgi stacks. Thus, our data reveal a fundamental role of GRASP65 in the integration of different stimuli to modulate Golgi structure and microtubule organization during cell division.
哺乳动物的高尔基体呈带状结构，位于中心体附近。尽管高尔基体具有多模块的组织形式，但它具有显著的结构可塑性，这在重要的生理过程中至关重要，例如细胞周期的 G2 期，在此期间，高尔基体带必须“解链”成独立的堆叠，以允许进入有丝分裂。在这里，我们表明，高尔基体相关蛋白 GRASP65 已知在高尔基体堆叠和带状形成中起作用，它对于微管细胞骨架的组织也是必需的。GRASP65 不参与微管的核形成或锚定。相反，它对于新核形成的微管的稳定是必需的，导致微管乙酰化和高尔基体堆叠的聚集。带状形成和微管稳定均受 JNK/ERK 介导的 GRASP65 的 S274 磷酸化调节，表明该蛋白可以协调高尔基体结构与微管组织。与重要作用一致，在细胞周期的 G2 期，微管乙酰化强烈减少，允许高尔基体堆叠的分离。因此，我们的数据揭示了 GRASP65 在整合不同刺激以调节细胞分裂过程中高尔基体结构和微管组织中的基本作用。
