Neurite outgrowth on a fibronectin isoform expressed during peripheral nerve regeneration is mediated by the interaction of paxillin with α4β1 integrins
| العنوان: | Neurite outgrowth on a fibronectin isoform expressed during peripheral nerve regeneration is mediated by the interaction of paxillin with α4β1 integrins |
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| المؤلفون: | Mark H. Ginsberg, Mariette G. Vogelezang, Ulrike B Forster, Charles ffrench-Constant, Jaewon Han |
| المساهمون: | Koch Institute for Integrative Cancer Research at MIT, Vogelezang, Mariette |
| المصدر: | BMC Neuroscience BMC neuroscience, vol 8, iss 1 BMC Neuroscience, Vol 8, Iss 1, p 44 (2007) Vogelezang, M, Forster, U B, Han, J, Ginsberg, M H & ffrench-Constant, C 2007, ' Neurite outgrowth on a fibronectin isoform expressed during peripheral nerve regeneration is mediated by the interaction of paxillin with alpha4beta1 integrins ', BMC Neuroscience, vol. 8, pp. 44 . https://doi.org/10.1186/1471-2202-8-44Test BioMed Central Ltd |
| بيانات النشر: | BioMed Central, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Neurite, Integrin, Growth Cones, GTPase, macromolecular substances, Integrin alpha4beta1, Regenerative Medicine, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cell Movement, Neurites, Animals, Peripheral Nerves, Phosphorylation, Growth cone, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Paxillin, 030304 developmental biology, 0303 health sciences, Neurology & Neurosurgery, biology, integumentary system, urogenital system, General Neuroscience, lcsh:QP351-495, Wild type, Neurosciences, Molecular biology, 3. Good health, Fibronectins, Nerve Regeneration, Rats, Fibronectin, lcsh:Neurophysiology and neuropsychology, Gene Expression Regulation, Neurological, embryonic structures, Mutation, biology.protein, Cognitive Sciences, sense organs, Biochemistry and Cell Biology, 030217 neurology & neurosurgery, Research Article |
| الوصف: | Background: The 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 α4β1 integrins that promote neurite outgrowth. Here we use PC12 cells to examine the role of the interaction between paxillin and the α4 integrin cytoplasmic domain in neurite outgrowth. Results: Expression of α4 with mutations in the paxillin-binding domain reduced neurite outgrowth on recombinant embryonic fibronectin fragments relative to wild type α4. 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 α4-mediated migration in leucocytes requires spatial regulation of α4 phosphorylation at Ser988, a post-translational modification that blocks paxillin binding to the integrin cytoplasmic domain. In keeping with this α4(S988D), which mimics phosphorylated α4, did not promote neurite outgrowth. However, α4 was not phosphorylated in the PC12 cells, and a non-phosphorylatable α4(S988A) mutant promoted neurite outgrowth indistinguishably from the wild type integrin. Conclusion: We establish the importance of the α4 integrin-paxillin interaction in a model of axonal regeneration and highlight differing dependence on phosphorylation of α4 for extension of neuronal growth cones and migration of non-neural cells. Action Medical Research National Institutes of Health (U.S.) (Grant AR27214) Arthritis Foundation Wellcome Trust (London, England) |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1471-2202 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa9da0eb9826b378614483bbc3e165a9Test http://europepmc.org/articles/PMC1940015Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fa9da0eb9826b378614483bbc3e165a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712202 |
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