期刊
JOURNAL OF NEUROSCIENCE
卷 30, 期 36, 页码 12185-12197出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1740-10.2010
关键词
-
资金
- National Institutes of Health [NS048090]
The initiation of axonal filopodia is the first step in the formation of collateral branches and synaptic structures. In sensory neurons, nerve growth factor (NGF) promotes the formation of axonal filopodia and branches. However, the signaling and cytoskeletal mechanisms of NGF-induced initiation of axonal filopodia are not clear. Axonal filopodia arise from precursor axonal cytoskeletal structures termed filamentous actin (F-actin) patches. Patches form spontaneously and are transient. Although filopodia emerge from patches, only a fraction of patches normally gives rise to filopodia. Using chicken sensory neurons and live imaging of enhanced yellow fluorescent protein (eYFP)-actin dynamics, we report that NGF promotes the formation of axonal filopodia by increasing the rate of F-actin patch formation but not the fraction of patches that give rise to filopodia. We also demonstrate that activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway is sufficient and required for driving the formation of axonal F-actin patches, filopodia, and axon branches. Using the green fluorescent protein-plekstrin homology domain of Akt, which targets to PI3K-generated phosphatidylinositol-3,4,5-triphosphate (PIP3), we report localized microdomains of PIP3 accumulation that form in synchrony with F-actin patches and that NGF promotes the formation of microdomains of PIP3 and patches. Finally, we find that, in NGF, F-actin patches form in association with axonal mitochondria and oxidative phosphorylation is required for patch formation. This investigation demonstrates that surprisingly NGFpromotes formation of axonal filopodia by increasing the formation of cytoskeletal filopodial precursors (patches) through localized microdomains of PI3K signaling but not the emergence of filopodia from patches.
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