Selective rab11 transport and the intrinsic regenerative ability of CNS axons.
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Authors
Koseki, Hiroaki
Donegá, Matteo
Lam, Brian Yh
Kwok, Jessica Cf
Ffrench-Constant, Charles
Publication Date
2017-08-08Journal Title
Elife
ISSN
2050-084X
Publisher
eLife Sciences Publications, Ltd
Volume
6
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Koseki, H., Donegá, M., Lam, B. Y., Petrova, V., van Erp, S., Yeo, G., Kwok, J. C., et al. (2017). Selective rab11 transport and the intrinsic regenerative ability of CNS axons.. Elife, 6 https://doi.org/10.7554/eLife.26956
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.
Keywords
Axons, Cytoplasmic Vesicles, Animals, Rats, Sprague-Dawley, rab GTP-Binding Proteins, Regeneration, Cell Differentiation, Biological Transport
Sponsorship
Medical Research Council (G1000864)
Spinal Research (ISRT) (NRB110)
International Foundation for Research in Paraplegia (IRP) (P172)
Medical Research Council (MR/R004544/1)
Medical Research Council (G0701518)
MRC (G1000864)
Identifiers
External DOI: https://doi.org/10.7554/eLife.26956
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275681
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