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

Accepted version
Peer-reviewed

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Authors

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

Abstract

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.

Description

Keywords

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

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
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)