A role for Arf1 in mitotic Golgi disassembly, chromosome segregation, and cytokinesis
A role for Arf1 in mitotic Golgi disassembly, chromosome segregation, and cytokinesis
复制标题
DOI：
10.1073/pnas.2234055100
复制
发表时间：
2003-11-11
影响因子：
11.1
通讯作者：
Lippincott-Schwartz, J
中科院分区：
文献类型：
--
作者：
Altan-Bonnet, N;Phair, RD;Lippincott-Schwartz, J
在有丝分裂中，染色体、细胞骨架和细胞器动力学必须协调一致才能成功细胞分裂。在这里，我们提供了 Arf1（一种与高尔基体相关的小型 GTP 酶）在有丝分裂高尔基体分解、染色体分离和胞质分裂中的作用的证据。我们发现，在有丝分裂早期，Arf1 变得不活跃并与高尔基膜分离。随后是大量 Arf1 依赖性外周高尔基体蛋白的分散和随后的高尔基体分解。如果通过小分子 H89 处理或表达其 GTP 锁定形式使 Arf1 保持活跃状态，则具有结合外周蛋白的完整高尔基体膜在整个有丝分裂过程中持续存在。这些细胞进入有丝分裂，但在染色体分离和细胞因子沟进入方面表现出严重缺陷。这些发现表明，有丝分裂高尔基体分解取决于 Arf1 失活，细胞利用 Arf1 分散大量外周高尔基体蛋白，以协调有丝分裂过程中高尔基体膜、染色体和细胞骨架的行为。
In mitosis, chromosome, cytoskeleton, and organelle dynamics must be coordinated for successful cell division. Here, we present evidence for a role for Arf1, a small GTPase associated with the Golgi apparatus, in the orchestration of mitotic Golgi breakdown, chromosome segregation, and cytokinesis. We show that early in mitosis Arf1 becomes inactive and dissociates from Golgi membranes. This is followed by the dispersal of numerous Arf1-dependent peripheral Golgi proteins and subsequent Golgi disassembly. If Arf1 is kept in an active state by treatment with the small molecule H89 or expression of its GTP-locked form, intact Golgi membranes with bound peripheral proteins persist throughout mitosis. These cells enter mitosis but exhibit gross defects in chromosome segregation and cytokinetic furrow ingression. These findings suggest that mitotic Golgi disassembly depends on Arf1 inactivation and is used by the cell to disperse numerous peripheral Golgi proteins for coordinating the behavior of Golgi membranes, chromosomes, and cytoskeleton during mitosis.