Koseki, H, Donega, M, Lam, BYH et al. (7 more authors) (2017) Selective rab11 transport and the intrinsic regenerative ability of CNS axons. eLife, 6. e26956. ISSN 2050-084X
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. Their transport changed from bidirectional to retrograde. 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Copyright Koseki et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
Keywords: | axon, growth cone, regeneration, axotomy, axon growth, trafficking, axonal transport, endosomes, small GTPases, Rabs, integrin, RNA sequencing |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 09 Aug 2017 09:43 |
Last Modified: | 13 Oct 2020 16:00 |
Status: | Published |
Publisher: | eLife Sciences Publications |
Identification Number: | 10.7554/eLife.26956 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119945 |