Journal article
Mechanism and role of the intra-axonal Calreticulin translation in response to axonal injury
EXPERIMENTAL NEUROLOGY, v 323, 113072
Jan 2020
PMID: 31669485
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Following injury, sensory axons locally translate mRNAs that encode proteins needed for the response to injury, locally and through retrograde signaling, and for regeneration. In this study, we addressed the mechanism and role of axotomy-induced intra-axonal translation of the ER chaperone Calreticulin. In vivo peripheral nerve injury increased Calreticulin levels in sensory axons. Using an in vitro model system of sensory neurons amenable to mechanistic dissection we provide evidence that axotomy induces local translation of Calreticulin through PERK (protein kinase RNA-like endoplasmic reticulum kinase) mediated phosphorylation of eIF2 alpha by a mechanism that requires both 5' and 3'UTRs (untranslated regions) elements in Calreticulin mRNA. ShRNA mediated depletion of Calreticulin or inhibition of PERK signaling increased axon retraction following axotomy. In contrast, expression of axonally targeted, but not somatically restricted, Calreticulin mRNA decreased retraction and promoted axon regeneration following axotomy in vitro. Collectively, these data indicate that the intra-axonal translation of Calreticulin in response to axotomy serves to minimize the ensuing retraction, and overexpression of axonally targeted Calreticulin mRNA promotes axon regeneration.
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Details
- Title
- Mechanism and role of the intra-axonal Calreticulin translation in response to axonal injury
- Publication Details
- EXPERIMENTAL NEUROLOGY, v 323, 113072
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE; SAN DIEGO
- Grant note
- We are thankful to Martinez-Salas E for sharing the plasmid pSuper.puro. This work was supported by the National Institutes of Health (NS078030 to GG).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000504802800019
- Scopus ID
- 2-s2.0-85074589298
- Other Identifier
- 991021860769704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences