Selective rab11 transport and the intrinsic regenerative ability of CNS axons

Koseki, Hiroaki, Donegá, Matteo, Lam, Brian Y. H., Petrova, Veselina, van Erp, Susan, Yeo, Giles S. H., Kwok, Jessica C. F., ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377, Eva, Richard and Fawcett, James W. (2017) Selective rab11 transport and the intrinsic regenerative ability of CNS axons. eLife, 6. ISSN 2050-084X

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Abstract

Neurons lose intrinsic axon regenerative ability with maturation, but the mechanism remains unclear. Using an in-vitro laser axotomy model, we show a progressive decline in the ability of cut CNS axons to form a new growth cone and then elongate. Failure of regeneration was associated with increased retraction after axotomy. Transportation into axons becomes selective with maturation; we hypothesized that selective exclusion of molecules needed for growth may contribute to regeneration decline. With neuronal maturity rab11 vesicles (which carry many molecules involved in axon growth) became selectively targeted to the somatodendritic compartment and excluded from axons by predominant retrograde transport However, on overexpression rab11 was mistrafficked into proximal axons, and these axons showed less retraction and enhanced regeneration after axotomy. These results suggest that the decline of intrinsic axon regenerative ability is associated with selective exclusion of key molecules, and that manipulation of transport can enhance regeneration.

Item Type: Article
Additional Information: Funding Information: 1John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom; 2Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; 3MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; 4MRC Centre of Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom; 5School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom; 6Centre of Reconstructive Neuroscience, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic Funding Information: The work was supported by grants from the Glaxo Smith Kline International Scholarship (to HK), Honjo International Scholarship (to HK), Bristol-Myers Squibb Graduate Studentship (to HK), the Christopher and Dana Reeve Foundation, the Medical Research Council, the ERC advanced grant ECMneuro, the NIHR Cambridge Biomedical Research Centre and the Operational Programme Research, Development and Education in the framework of the project ‘Centre of Reconstructive Neuroscience’, registration number CZ.02.1.01/0.0./0.0/15_003/0000419
Uncontrolled Keywords: neuroscience(all),immunology and microbiology(all),biochemistry, genetics and molecular biology(all) ,/dk/atira/pure/subjectarea/asjc/2800
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 15 Jul 2022 14:31
Last Modified: 12 Aug 2022 05:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/86237
DOI: 10.7554/eLife.26956

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