期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 36, 页码 13205-13210出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1400737111
关键词
-
资金
- German Research Foundation [SPP1365/KA3423/1-1, SFB958/A16]
- Fritz Thyssen Foundation
- Japan Society for the Promotion of Science (Postdoctoral Fellowship for Research Abroad)
- Yamanouchi Foundation for Research on Metabolic Disorders
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Max Planck Society
- Vlaams Instituut voor Biotechnologie
- Onderzoekstoelage [OT/12/089]
- NIH-National Institute of Neurological Disorders and Stroke [NS089456]
- HEALTH-2009-2.1.2-1 EU-FP7 SynSys
- MRC [G0802289] Funding Source: UKRI
- Medical Research Council [G0802289] Funding Source: researchfish
Protein ubiquitination is a core regulatory determinant of neural development. Previous studies have indicated that the Nedd4-family E3 ubiquitin ligases Nedd4-1 and Nedd4-2 may ubiquitinate phosphatase and tensin homolog (PTEN) and thereby regulate axonal growth in neurons. Using conditional knockout mice, we show here that Nedd4-1 and Nedd4-2 are indeed required for axonal growth in murine central nervous system neurons. However, in contrast to previously published data, we demonstrate that PTEN is not a substrate of Nedd4-1 and Nedd4-2, and that aberrant PTEN ubiquitination is not involved in the impaired axon growth upon deletion of Nedd4-1 and Nedd4-2. Rather, PTEN limits Nedd4-1 protein levels by modulating the activity of mTORC1, a protein complex that controls protein synthesis and cell growth. Our data demonstrate that Nedd4-family E3 ligases promote axonal growth and branching in the developing mammalian brain, where PTEN is not a relevant substrate. Instead, PTEN controls neurite growth by regulating Nedd4-1 expression.
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