Nerve growth factor induces axonal filopodia through localized microdomains of phosphoinositide 3-kinase activity that drive the formation of cytoskeletal precursors to filopodia.
Nerve growth factor induces axonal filopodia through localized microdomains of phosphoinositide 3-kinase activity that drive the formation of cytoskeletal precursors to filopodia.
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DOI：
10.1523/jneurosci.1740-10.2010
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发表时间：
2010-09-08
期刊：
影响因子：
--
通讯作者：
Gallo G
中科院分区：
文献类型：
--
作者：
Ketschek A;Gallo G
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 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 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 PI3K-Akt pathway is sufficient and required for driving the formation of axonal F-actin patches, filopodia and axon branches. Using the GFP-PH domain of Akt, which targets to PI3K-generated 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 NGF promotes 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.
