Ran is an evolutionarily conserved eukaryotic GTPase that directly participates in cell cycle and whose loss affects many biological processes.We have identified cDNA of TaRAN/,a novel Ran GTPase homologous gene in wh...Ran is an evolutionarily conserved eukaryotic GTPase that directly participates in cell cycle and whose loss affects many biological processes.We have identified cDNA of TaRAN/,a novel Ran GTPase homologous gene in wheat(Triticum aestivum L.cv.Jingdong No.1).The cytoplasmic microtu-bules play an important role in cytoplasmic organization,cell division,and the correct transmission of genetic information in fission yeast cell.Using the fission yeast system in vivo experiments,overexpression of TaRAN/produced defective spindle microtubules,probably resulting in chromosome missegregation we reported previously.The microtubules of antisense TaRANI yeast cells were physically disrupted.This suggested that TaRAN/plays a role in mitotic spindle assembly and microtubule integrity and stability.Ultrastructural analysis under transmission electron microscope(TEM)showed abnormal nuclear membranes in the overexpression TaRAN/yeast cells,abnormal vacuole structures and disorganized membranes in the antisense TaRANI yeast cells.These results suggested that TaRANI was essential for all nucleocytoplasmic transport events.展开更多
Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. The Ran GTPase plays a key role in mitotic spindle assembly. However, how the gene...Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. The Ran GTPase plays a key role in mitotic spindle assembly. However, how the generation of a chemical gradient of Ran-GTP at the spindle is coupled to mitotic post-translational modifications has never been characterized. Here, we solved the complex structure of Ran with the nucleotide release factor Mogl and delineated a novel mitosis-specific acetylation-regulated Ran-Mogl interaction dur- ing chromosome segregation. Our structure-guided functional analyses revealed that Mogl compotes with RCCl for Ran binding in a GTP/GDP-dependent manner. Biochemical characterization demonstrated that Mogl-bound Ran prevents RCCl binding and subse- quent GTP loading. Surprisingly, Ran is a bono fide substrate of TIP60, and the acetylation of Lys134 by TIP60 liberates Mogl from Ran binding during mitosis. Importantly, this acetylation-elicited switch of Ran binding to RCC1 promotes high level of Ran-GTP, which is essential for chromosome alignment. These results establish a previously uncharacterized regulatory mechanism in which TIP60 pro- vides a homeostatic control of Ran-GTP level by tuning Ran effector binding for chromosome segregation in mitosis.展开更多
文摘Ran is an evolutionarily conserved eukaryotic GTPase that directly participates in cell cycle and whose loss affects many biological processes.We have identified cDNA of TaRAN/,a novel Ran GTPase homologous gene in wheat(Triticum aestivum L.cv.Jingdong No.1).The cytoplasmic microtu-bules play an important role in cytoplasmic organization,cell division,and the correct transmission of genetic information in fission yeast cell.Using the fission yeast system in vivo experiments,overexpression of TaRAN/produced defective spindle microtubules,probably resulting in chromosome missegregation we reported previously.The microtubules of antisense TaRANI yeast cells were physically disrupted.This suggested that TaRAN/plays a role in mitotic spindle assembly and microtubule integrity and stability.Ultrastructural analysis under transmission electron microscope(TEM)showed abnormal nuclear membranes in the overexpression TaRAN/yeast cells,abnormal vacuole structures and disorganized membranes in the antisense TaRANI yeast cells.These results suggested that TaRANI was essential for all nucleocytoplasmic transport events.
文摘Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. The Ran GTPase plays a key role in mitotic spindle assembly. However, how the generation of a chemical gradient of Ran-GTP at the spindle is coupled to mitotic post-translational modifications has never been characterized. Here, we solved the complex structure of Ran with the nucleotide release factor Mogl and delineated a novel mitosis-specific acetylation-regulated Ran-Mogl interaction dur- ing chromosome segregation. Our structure-guided functional analyses revealed that Mogl compotes with RCCl for Ran binding in a GTP/GDP-dependent manner. Biochemical characterization demonstrated that Mogl-bound Ran prevents RCCl binding and subse- quent GTP loading. Surprisingly, Ran is a bono fide substrate of TIP60, and the acetylation of Lys134 by TIP60 liberates Mogl from Ran binding during mitosis. Importantly, this acetylation-elicited switch of Ran binding to RCC1 promotes high level of Ran-GTP, which is essential for chromosome alignment. These results establish a previously uncharacterized regulatory mechanism in which TIP60 pro- vides a homeostatic control of Ran-GTP level by tuning Ran effector binding for chromosome segregation in mitosis.
