ArticleBMC neuroscience2007
Neurite outgrowth on a fibronectin isoform expressed during peripheral nerve regeneration is mediated by the interaction of paxillin with alpha4beta1 integrins.
Article in BMC neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Augmenting fibronectin levels in injured adult CNS promotes axon regeneration in vivo.Experimental neurology · 2024Article
- Article
- Early Synaptic Alterations and Selective Adhesion Signaling in Hippocampal Dendritic Zones Following Organophosphate Exposure.Scientific reports · 2019Article
- SSeCKS promoted lipopolysaccharide-sensitized astrocytes migration via increasing β-1,4-galactosyltransferase-I activity.Neurochemical research · 2019Article
- Integrins promote axonal regeneration after injury of the nervous system.Biological reviews of the Cambridge Philosophical Society · 2018Review
- Exclusion of integrins from CNS axons is regulated by Arf6 activation and the AIS.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- A cell-assembled, spatially aligned extracellular matrix to promote directed tissue development.Journal of materials chemistry. B · 2014Article
- Extracellular matrix-associated gene expression in adult sensory neuron populations cultured on a laminin substrate.BMC neuroscience · 2013Article
- Proregenerative properties of ECM molecules.BioMed research international · 2013Review
- Fibronectin supports neurite outgrowth and axonal regeneration of adult brain neurons in vitro.Brain research · 2012Article
- Spatial phosphoprotein profiling reveals a compartmentalized extracellular signal-regulated kinase switch governing neurite growth and retraction.The Journal of biological chemistry · 2011Article
- Alpha9 integrin promotes neurite outgrowth on tenascin-C and enhances sensory axon regeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe regeneration of peripheral nerve is associated with a change in the alternative splicing of the fibronectin primary gene transcript to re-express embryonic isoforms containing a binding site for alpha4beta1 integrins that promote neurite outgrowth. Here we use PC12 cells to examine the role of the interaction between paxillin and the alpha4 integrin cytoplasmic domain in neurite outgrowth.
resultsExpression of alpha4 with mutations in the paxillin-binding domain reduced neurite outgrowth on recombinant embryonic fibronectin fragments relative to wild type alpha4. Over-expression of paxillin promoted neurite outgrowth while a mutant isoform lacking the LD4 domain implicated in the regulation of ARF and Rac GTPases was less effective. Optimal alpha4-mediated migration in leucocytes requires spatial regulation of alpha4 phosphorylation at Ser988, a post-translational modification that blocks paxillin binding to the integrin cytoplasmic domain. In keeping with this alpha4(S988D), which mimics phosphorylated alpha4, did not promote neurite outgrowth. However, alpha4 was not phosphorylated in the PC12 cells, and a non-phosphorylatable alpha4(S988A) mutant promoted neurite outgrowth indistinguishably from the wild type integrin.
conclusionWe establish the importance of the alpha4 integrin-paxillin interaction in a model of axonal regeneration and highlight differing dependence on phosphorylation of alpha4 for extension of neuronal growth cones and migration of non-neural cells.
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Registered trials
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