Repository logo

Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS.

Accepted version

Change log


Pearson, Craig S 
Ching, Jared 
Tribble, James R 
Solano, Andrea G 


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.



Animals, Axons, Cells, Cultured, Central Nervous System, Endoplasmic Reticulum, Endosomes, Female, Humans, Integrins, Mice, Mice, Inbred C57BL, Mutation, Nerve Regeneration, Neurons, Neuroprotective Agents, Optic Nerve Injuries, Phosphorylation, Protein Domains, Rats, Rats, Sprague-Dawley, Retina, Vesicular Transport Proteins

Journal Title

Nat Commun

Conference Name

Journal ISSN


Volume Title



Springer Science and Business Media LLC


All rights reserved
Wellcome Trust (082381/Z/07/Z)
Medical Research Council (MR/R004463/1)
Social Sciences and Humanities Research Council of Canada (SSHRC) (via McGill University) (Unknown)
Cambridge Eye Trust (unknown)
Wellcome Trust (104001/Z/14/Z)
Medical Research Council (MR/R004544/1)
Fight for Sight (5119 / 5120)
Funding was from the UK Medical Research Council (MR/R004544/1, MR/R004463/1)