Robo3.1A suppresses Slit-mediated repulsion by triggering degradation of Robo2
文献类型：期刊论文
| 作者 | Li, Lingyong1,2; Liu, Shengbing3; Lei, Yun1,2; Cheng, Ye4; Yao, Changqun1,2; Zhen, Xuechu1,2 |
| 刊名 | JOURNAL OF NEUROSCIENCE RESEARCH
 |
| 出版日期 | 2014-07 |
| 卷号 | 92期号:7页码:835-846 |
| 关键词 | Robo2 axon guidance Slit Robo3 degradation |
| ISSN号 | 0360-4012 |
| DOI | 10.1002/jnr.23364 |
| 文献子类 | Article |
| 英文摘要 | Slits and Robos control the midline crossing of commissural axons, which are not sensitive to the midline repellent Slit before crossing but gain Slit responsiveness to exit the midline and avoid recrossing. Robo3.1A promotes midline crossing of commissural axons by suppressing the axonal responsiveness to the midline repellent Slit, but the underlying mechanism remains unclear. By using a cell surface binding assay and immunoprecipitation, we observed that Robo3.1A did not bind Slit on its own but prevented the specific binding of Slit to the cell surface when it was coexpressed with its close homologue Robo1 or Robo2 (Robo1/2), which are known to mediate the Slit repulsion. Cotransfection with Robo3.1A significantly reduced the protein level of Robo2 in HEK293 cells, and overexpression of Robo3.1A also significantly decreased Robo2 protein level in cerebellar granule cells. Downregulation of endogenous Robo3 by specific small interference RNA (siRNA) significantly increased Robo1 protein level, Slit binding to the cell surface was significantly elevated, and Slit-triggered growth cone collapse appeared after downregulation of Robo3 in cultured cortical neurons. Immunocytochemical staining showed that Robo2 and Robo3 colocalized in intracellular vesicles positive for the marker of late endosomes and lysosomes, but not trans-Golgi apparatus and early endosomes. Thus Robo3.1A may prevent the Slit responsiveness by recruiting Robo1/2 into a late endosome- and lysosome-dependent degradation pathway. (c) 2014 Wiley Periodicals, Inc. |
| WOS关键词 | HORIZONTAL GAZE PALSY ; AXON GUIDANCE ; PROGRESSIVE SCOLIOSIS ; COMMISSURAL AXONS ; CNS MIDLINE ; SPINAL-CORD ; GROWTH CONE ; IN-VIVO ; MUTATIONS ; PROTEIN |
| 资助项目 | Natural Science Foundation of China[30900461] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000335704400003 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277017]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Li, Lingyong |
| 作者单位 | 1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Dept Pharmacol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Jiaxing Univ, Dept Histol & Embryol, Coll Med, Jiaxing, Zhejiang, Peoples R China; 4.Second Mil Med Univ, Dept Nephrol, Changzheng Hosp, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Lingyong,Liu, Shengbing,Lei, Yun,et al. Robo3.1A suppresses Slit-mediated repulsion by triggering degradation of Robo2[J]. JOURNAL OF NEUROSCIENCE RESEARCH,2014,92(7):835-846. |
| APA | Li, Lingyong,Liu, Shengbing,Lei, Yun,Cheng, Ye,Yao, Changqun,&Zhen, Xuechu.(2014).Robo3.1A suppresses Slit-mediated repulsion by triggering degradation of Robo2.JOURNAL OF NEUROSCIENCE RESEARCH,92(7),835-846. |
| MLA | Li, Lingyong,et al."Robo3.1A suppresses Slit-mediated repulsion by triggering degradation of Robo2".JOURNAL OF NEUROSCIENCE RESEARCH 92.7(2014):835-846. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。