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, C; Liang, XJ; Ma, L; Yuan, XB; Zhu, XL |
| 刊名 | JOURNAL OF CELL SCIENCE
 |
| 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 |
| 通讯作者 | Zhu, X (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 |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | PLATELET-ACTIVATING-FACTOR ; ACETYLHYDROLASE CATALYTIC SUBUNITS ; NEURONAL MIGRATION DEFECTS ; DIEKER LISSENCEPHALY GENE ; EARLY EMBRYONIC LETHALITY ; MITOTIC SPINDLE ; PROTEIN-TRANSPORT ; MOTOR FUNCTION ; CELL-DIVISION ; NUDEL |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000268727400005 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1277]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Ding, C,Liang, XJ,Ma, L,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, C,Liang, XJ,Ma, L,Yuan, XB,&Zhu, XL.(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, C,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. |
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