Neurotrophins Support Regenerative Axon Assembly over Cspgs by an Ecm-integrin-independent Mechanism.
From: Neuroscience Center, 8109 Neuroscience Research Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Journal of cell science
- Publish Date: Jul 2006
- ISSN: 0021-9533
- Volume: 119
- Issue: Pt 13
- Pages: 2787-96
- Medium: Print
- Language: English
- Citation (JAMA): Zhou Feng-Quan, Walzer Mark, Wu Yao-Hong, et al. Neurotrophins Support Regenerative Axon Assembly over Cspgs by an Ecm-integrin-independent Mechanism.. J. Cell. Sci. Jul 2006;119:2787-96
Abstract
Chondroitin sulfate proteoglycans (CSPGs) and myelin-based inhibitors are the most studied inhibitory molecules in the adult central nervous system. Unlike myelin-based inhibitors, few studies have reported ways to overcome the inhibitory effect of CSPGs. Here, by using regenerating adult dorsal root ganglion (DRG) neurons, we show that chondroitin sulfate proteoglycans inhibit axon assembly by a different mechanism from myelin-based inhibitors. Furthermore, we show that neither Rho inhibition nor cAMP elevation rescues extracellular factor-induced axon assembly inhibited by CSPGs. Instead, our data suggest that CSPGs block axon assembly by interfering with integrin signaling. Surprisingly, we find that nerve growth factor (NGF) promotes robust axon growth of regenerating DRG neurons over CSPGs. We have found that, unlike naive neurons that require simultaneous activation of neurotrophin and integrin pathways for axon assembly, either neurotrophin or integrin signaling alone is sufficient to induce axon assembly of regenerating neurons. Thus, our results suggest that the ability of NGF to overcome CSPG inhibition in regenerating neurons is probably due to the ability of regenerating neurons to assemble axons using an integrin-independent pathway. Finally, our data show that the GSK-3beta-APC pathway, previously shown to mediate developing axon growth, is also necessary for axon regeneration.
Mesh Headings (Keywords): Aggrecans, Animals, Axons, Cells, Cultured, Extracellular Matrix, Extracellular Matrix Proteins, Ganglia, Spinal, Integrins, Lectins, C-Type, Mice, Models, Biological, Myelin Proteins, Nerve Growth Factor, Nerve Growth Factors, Nerve Regeneration, Neurons, Proteochondroitin Sulfates, Retrograde Degeneration, Signal Transduction, rho GTP-Binding Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16772333
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