Opposing effects of Ndel1 and alpha 1 or alpha 2 on cytoplasmic dynein through competitive binding to Lis1
文献类型:期刊论文
作者 | Ding, Chong ; Liang, Xujun ; Ma, Li ; Yuan, Xiaobing ; Zhu, Xueliang |
刊名 | JOURNAL OF CELL SCIENCE
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出版日期 | 2009 |
卷号 | 122期号:16页码:2820-2827 |
关键词 | Nudel Cytoplasmic dynein Mitosis Neuronal migration Platelet-activating factor acetylhydrolase (PAF-AH) Ib complex Vesicle transport PLATELET-ACTIVATING-FACTOR ACETYLHYDROLASE CATALYTIC SUBUNITS NEURONAL MIGRATION DEFECTS DIEKER LISSENCEPHALY GENE EARLY EMBRYONIC LETHALITY MITOTIC SPINDLE PROTEIN-TRANSPORT MOTOR FUNCTION CELL-DIVISION NUDEL |
ISSN号 | 0021-9533 |
通讯作者 | Zhu, XL (reprint author), Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,xlzhu@sibs.ac.cn |
英文摘要 | Lis1 is an essential protein whose insufficiency causes aberrant neuronal positioning during neocortical development. It is believed to regulate both cytoplasmic dynein, a microtubule minus-end-directed motor, through direct interaction, and platelet-activating factor acetylhydrolase (PAF-AH) Ib by complexing with the catalytic subunits alpha 1 and alpha 2. Although alpha 1 and alpha 2 are highly expressed in brain, their deficiencies fail to cause brain abnormality. Here, we show that overexpression of alpha 2 or alpha 1 results in inactivation of dynein characterized by Golgi and endosome dispersion and mitotic delay. Further overexpression of Lis1 or Ndel1, a Lis1- and dynein-binding protein that is also crucial for dynein function, restored Golgi and endosome distribution. Biochemical assays showed that alpha 1 and especially alpha 2, were able to compete against Ndel1 and dynein for Lis1 binding in a dose-dependent manner. Overexpression of alpha 2 in developing rat brain repressed the radial migration of neurons and mitotic progression of neuroprogenitors. By contrast, a Lis1-binding-defective point mutant, alpha 2(E39D), was ineffective in the above assays. These results indicate an antagonistic effect of alpha 1, alpha 2 and Ndel1 for Lis1 binding, probably to modulate dynein functions in vivo. They also help to explain why brain development is particularly sensitive to a decrease in Lis1 levels. |
学科主题 | Cell Biology |
收录类别 | SCI |
资助信息 | National Science Foundation of China[30721065, 30830060, 30623003, 30771076]; Ministry of Science and Technology of China[2005CB522701, 2006CB943900, 2007CB914501, 2007CB947100]; Science and Technology Commission of Shanghai Municipality[08XD14048, 088014199]; Chinese Academy of Sciences[KSCX2-YW-R-108] |
语种 | 英语 |
公开日期 | 2012-07-13 |
源URL | [http://ir.sibs.ac.cn/handle/331001/1647] ![]() |
专题 | 上海神经科学研究所_神经所(总) |
推荐引用方式 GB/T 7714 | Ding, Chong,Liang, Xujun,Ma, Li,et al. Opposing effects of Ndel1 and alpha 1 or alpha 2 on cytoplasmic dynein through competitive binding to Lis1[J]. JOURNAL OF CELL SCIENCE,2009,122(16):2820-2827. |
APA | Ding, Chong,Liang, Xujun,Ma, Li,Yuan, Xiaobing,&Zhu, Xueliang.(2009).Opposing effects of Ndel1 and alpha 1 or alpha 2 on cytoplasmic dynein through competitive binding to Lis1.JOURNAL OF CELL SCIENCE,122(16),2820-2827. |
MLA | Ding, Chong,et al."Opposing effects of Ndel1 and alpha 1 or alpha 2 on cytoplasmic dynein through competitive binding to Lis1".JOURNAL OF CELL SCIENCE 122.16(2009):2820-2827. |
入库方式: OAI收割
来源:上海神经科学研究所
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