Altan-Bonnet Nihal, Phair Robert D, Polishchuk Roman S, Weigert Roberto, Lippincott-Schwartz Jennifer
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13314-9. doi: 10.1073/pnas.2234055100. Epub 2003 Oct 29.
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.
在有丝分裂过程中,染色体、细胞骨架和细胞器动力学必须协调一致才能成功进行细胞分裂。在此,我们提供证据表明,一种与高尔基体相关的小GTP酶Arf1在有丝分裂期高尔基体解体、染色体分离和胞质分裂的协调过程中发挥作用。我们发现,在有丝分裂早期,Arf1变得无活性并从高尔基体膜上解离。随后,众多依赖Arf1的高尔基体周边蛋白分散,接着高尔基体解体。如果通过小分子H89处理或表达其GTP锁定形式使Arf1保持活性状态,带有结合周边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,但在染色体分离和胞质分裂沟侵入方面表现出严重缺陷。这些发现表明,有丝分裂期高尔基体解体依赖于Arf1失活,并且细胞利用这一过程分散众多高尔基体周边蛋白,以在有丝分裂期间协调高尔基体膜、染色体和细胞骨架的行为。