期刊
NEUROBIOLOGY OF DISEASE
卷 40, 期 1, 页码 222-237出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.05.029
关键词
L1 CAM; Protein trafficking; Cell surface expression; ER export; ER stress; Axon growth; Axonal targeting; Neural development; Neurological disorder; Hippocampus
资金
- Deutsche Forschungsgemeinschaft [SFB780, SCHA1261/1-1, Br1217/3-1]
- Landesgraduiertenforderung Baden-Wurttem-berg
- Medical Faculty of the University of Freiburg [SCH629/08]
Mutations in the human L1CAM gene cause neurodevelopmental disorders collectively referred to as L1 syndrome. Here, we investigated cellular pathomechanisms underlying two L1 syndrome mutations, R184Q and W1036L We demonstrate that these mutations cause partial endoplasmic reticulum (ER) retention of L1, reduce L1 cell surface expression, but do not induce ER stress in neuronal NSC-34 cells. We provide evidence that surface trafficking of mutated L1 is affected by defective sorting to ER exit sites and attenuated ER export. However, in differentiated neuronal cultures and long-term cultured hippocampal slices, the L1-R184Q protein is restricted to cell bodies, whereas L1-W1036L also aberrantly localizes to dendrites. These trafficking defects preclude axonal targeting of L1, thereby affecting L1-mediated axon growth and arborization. Our results indicate that L1 syndrome mutations impair neuronal L1 function at different levels, firstly by attenuating ER export and secondly by interfering with polarized neuronal trafficking. (c) 2010 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据