Selective rab11 transport and the intrinsic regenerative ability of CNS axons.


Type
Article
Change log
Authors
Koseki, Hiroaki 
Donegá, Matteo 
Lam, Brian Yh 
Petrova, Veselina 
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.

Description
Keywords
axon regeneration, axonal transport, axotomy, endosomes, human, neuroscience, rat, small GTPases, trafficking, Animals, Axons, Biological Transport, Cell Differentiation, Cytoplasmic Vesicles, Rats, Sprague-Dawley, Regeneration, rab GTP-Binding Proteins
Journal Title
Elife
Conference Name
Journal ISSN
2050-084X
2050-084X
Volume Title
6
Publisher
eLife Sciences Publications, Ltd
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)