Selective rab11 transport and the intrinsic regenerative ability of CNS axons

0481164 - ÚEM 2018 RIV GB eng J - Journal Article
Koseki, H. - Donegá, M. - Lam, B.Y.H. - Petrová, V. - van Erp, S. - Yeo, G.S.H. - Kwok, Jessica - Ffrench-Constant, Ch. - Eva, R. - Fawcett, James
Selective rab11 transport and the intrinsic regenerative ability of CNS axons.
eLife. Roč. 6, aug (2017), e26956. ISSN 2050-084X. E-ISSN 2050-084X
R&D Projects: GA MŠMT(CZ) EF15_003/0000419
Institutional support: RVO:68378041
Keywords : spinal-cord-injury * chondroitin sulfate proteoglycans * growth cone
OECD category: Neurosciences (including psychophysiology
Impact factor: 7.616, year: 2017

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.
Permanent Link: http://hdl.handle.net/11104/0276768