Hydrogen peroxide is a neuronal alarmin that triggers specific RNAs, local translation of Annexin A2, and cytoskeletal remodeling in Schwann cells.
Samuele NegroMarco StaziMarta MarchiorettoToma TebaldiUmberto RodellaElisa DuregottiVolker GerkeAlessandro QuattroneCesare MontecuccoMichela RigoniGabriella VieroPublished in: RNA (New York, N.Y.) (2018)
Schwann cells are key players in neuro-regeneration: They sense "alarm" signals released by degenerating nerve terminals and differentiate toward a proregenerative phenotype, with phagocytosis of nerve debris and nerve guidance. At the murine neuromuscular junction, hydrogen peroxide (H2O2) is a key signal of Schwann cells' activation in response to a variety of nerve injuries. Here we report that Schwann cells exposed to low doses of H2O2 rewire the expression of several RNAs at both transcriptional and translational levels. Among the genes positively regulated at both levels, we identified an enriched cluster involved in cytoskeleton remodeling and cell migration, with the Annexin (Anxa) proteins being the most represented family. We show that both Annexin A2 (Anxa2) transcript and protein accumulate at the tips of long pseudopods that Schwann cells extend upon H2O2 exposure. Interestingly, Schwann cells reply to this signal and to nerve injury by locally translating Anxa2 in pseudopods, and undergo an extensive cytoskeleton remodeling. Our results show that, similarly to neurons, Schwann cells take advantage of local protein synthesis to change shape and move toward damaged axonal terminals to facilitate axonal regeneration.
Keyphrases
- induced apoptosis
- cell cycle arrest
- peripheral nerve
- hydrogen peroxide
- stem cells
- endoplasmic reticulum stress
- cell death
- spinal cord injury
- nitric oxide
- gene expression
- cell migration
- transcription factor
- oxidative stress
- dna methylation
- long non coding rna
- single cell
- blood brain barrier
- binding protein
- cell proliferation
- rna seq
- amino acid