ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Atypical protein kinase C and Par3 are required for proteoglycan-induced axon growth inhibition.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders.Frontiers in cellular neuroscience · 2023Review
- Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system.Nature communications · 2022Article
- Liver Kinase B1 Functions as a Regulator for Neural Development and a Therapeutic Target for Neural Repair.Cells · 2022Review
- The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Review
- Extracellular Matrix in Neural Plasticity and Regeneration.Cellular and molecular neurobiology · 2022Review
- Cellular and Molecular Gradients in the Ventral Horns With Increasing Distance From the Injury Site After Spinal Cord Contusion.Frontiers in cellular neuroscience · 2022Article
- Article
- Depletion of senescent-like neuronal cells alleviates cisplatin-induced peripheral neuropathy in mice.Scientific reports · 2020Article
- Glial Scar-a Promising Target for Improving Outcomes After CNS Injury.Journal of molecular neuroscience : MN · 2020Review
- Advances in the Signaling Pathways Downstream of Glial-Scar Axon Growth Inhibitors.Frontiers in cellular neuroscience · 2020Review
- Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration.Frontiers in neuroscience · 2020Review
- aPKC in neuronal differentiation, maturation and function.Neuronal signaling · 2019Review
- Article
- Two PTP receptors mediate CSPG inhibition by convergent and divergent signaling pathways in neurons.Scientific reports · 2016Article
- The reactions and role of NG2 glia in spinal cord injury.Brain research · 2016Review
- Molecular mechanisms of scar-sourced axon growth inhibitors.Brain research · 2015Review
- Transduction of extracellular cues into cell polarity: the role of the transmembrane proteoglycan NG2.Molecular neurobiology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When the CNS is injured, damaged axons do not regenerate. This failure is due in part to the growth-inhibitory environment that forms at the injury site. Myelin-associated molecules, repulsive axon guidance molecules, and extracellular matrix molecules including chondroitin sulfate proteoglycans (CSPGs) found within the glial scar inhibit axon regeneration but the intracellular signaling mechanisms triggered by these diverse molecules remain largely unknown. Here we provide biochemical and functional evidence that atypical protein kinase C (PKCζ) and polarity (Par) complex proteins mediate axon growth inhibition. Treatment of postnatal rat neurons in vitro with the NG2 CSPG, a major component of the glial scar, activates PKCζ, and this activation is both necessary and sufficient to inhibit axonal growth. NG2 treatment also activates Cdc42, increases the association of Par6 with PKCζ, and leads to a Par3-dependent activation of Rac1. Transfection of neurons with kinase-dead forms of PKCζ, dominant-negative forms of Cdc42, or mutant forms of Par6 that do not bind to Cdc42 prevent NG2-induced growth inhibition. Similarly, transfection with either a phosphomutant Par3 (S824A) or dominant-negative Rac1 prevent inhibition, whereas expression of constitutively active Rac1 inhibits axon growth on control surfaces. These results suggest a model in which NG2 binding to neurons activates PKCζ and modifies Par complex function. They also identify the Par complex as a novel therapeutic target for promoting axon regeneration after CNS injury.
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