Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin's endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system.
- MeSH
- axony metabolismus fyziologie MeSH
- centrální nervový systém fyziologie MeSH
- endoplazmatické retikulum genetika metabolismus MeSH
- endozomy metabolismus MeSH
- fosforylace MeSH
- integriny metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mutace MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neurony metabolismus fyziologie MeSH
- neuroprotektivní látky aplikace a dávkování MeSH
- poranění nervus opticus farmakoterapie metabolismus patologie MeSH
- potkani Sprague-Dawley MeSH
- proteinové domény MeSH
- regenerace nervu * účinky léků MeSH
- retina účinky léků fyziologie MeSH
- vezikulární transportní proteiny aplikace a dávkování chemie genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH