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Journal article
Nerve Growth Factor-Induced Formation of Axonal Filopodia and Collateral Branches Involves the Intra-Axonal Synthesis of Regulators of the Actin-Nucleating Arp2/3 Complex
The Journal of neuroscience, v 32(49), pp 17671-17689
05 Dec 2012
PMID: 23223289
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Nerve growth factor (NGF) induces collateral branching along sensory axons by promoting the formation of axonal filopodia dependent on the actin-nucleating Arp2/3 complex. This study shows that chicken embryonic sensory axons contain mRNAs for the actin-nucleating Arp2/3 complex activator WAVE1 and the complex stabilizer cortactin. NGF increases the axonal levels of WAVE1 and cortactin through localized protein synthesis even in axons isolated from the cell body. Inhibition of protein synthesis in severed axons impairs NGF-induced branching, the formation of axonal filopodia, and the initiation of Arp2/3-dependent axonal actin patches, which serve as precursors to the emergence of filopodia. Overexpression of WAVE1 or cortactin in axons not treated with NGF increased the rate of actin patch formation and the frequency of the emergence of filopodia from actin patches, respectively. Antisense inhibition of cortactin mRNA translation in isolated axons blocked NGF-induced filopodia. NGF also activated the Rac1 GTPase, which drives WAVE1 activity, in a protein synthesis-independent manner. Similarly, inhibition of protein synthesis did not impair the effects of NGF on the axonal microtubule cytoskeleton during branching. The effects of NGF on Rac1 activity and increases in axonal levels of WAVE1 and cortactin were both dependent on phosphoinositide 3-kinase (PI3K) signaling. Collectively, the data indicate that NGF promotes sensory axon branching through regulation of the actin cytoskeleton using both canonical signaling mechanisms and intra-axonal protein synthesis downstream of PI3K signaling. Finally, we present experimental evidence of axonal mRNA translation in sensory axons in the living embryonic spinal cord.
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Details
- Title
- Nerve Growth Factor-Induced Formation of Axonal Filopodia and Collateral Branches Involves the Intra-Axonal Synthesis of Regulators of the Actin-Nucleating Arp2/3 Complex
- Creators
- Mirela Spillane - Drexel UniversityAndrea Ketschek - Temple Univ, Shriners Hosp Pediat Res Ctr, Dept Anat & Cell Biol, Philadelphia, PA 19140 USAChris J. Donnelly - University of DelawareAlmudena Pacheco - Drexel UniversityJeffrey L. Twiss - Drexel UniversityGianluca Gallo - Drexel University
- Publication Details
- The Journal of neuroscience, v 32(49), pp 17671-17689
- Publisher
- Soc Neuroscience
- Number of pages
- 19
- Grant note
- NS048090; R01-NS041596 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01NS041596 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000312402200014
- Scopus ID
- 2-s2.0-84870551021
- Other Identifier
- 991021892011004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences