Abstract
Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury or disease have permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules. We achieved this by expressing the adaptor molecule Protrudin which enabled robust central nervous system regeneration both in vitro and in vivo in the injured adult optic nerve. Protrudin expression facilitated the accumulation of endoplasmic reticulum and Rab11 endosomes in the distal axon, whereas 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.
One Sentence Summary Protrudin promotes axon regeneration in the adult central nervous system through the mobilization of subcellular machinery.