Retinoic acid regulates Schwann cell migration via NEDD9 induction by transcriptional and post-translational mechanisms

Biochim Biophys Acta. 2016 Jul;1863(7 Pt A):1510-8. doi: 10.1016/j.bbamcr.2016.04.009. Epub 2016 Apr 13.


Schwann cell migration is essential during the regenerative response to nerve injury, however, the factors that regulate this phenomenon are not yet clear. Here we describe that retinoic acid (RA), whose production and signaling activity are greatly enhanced during nerve regeneration, increases Schwann cell migration. This is accompanied by the up-regulation of NEDD9, a member of the CAS family of scaffold proteins previously implicated in migratory and invasive behavior in gliomas, melanomas and the neural crest cells from which Schwann cells derive. This RA-induced NEDD9 accumulation is due to augmented mRNA levels, as well as an increase of NEDD9 protein stability. Although all NEDD9 phospho-isoforms present in Schwann cells are induced by the retinoid, the hormone also changes its phosphorylation status, thus altering the ratio between the different isoforms. Silencing NEDD9 in Schwann cells had no effect on basal migratory ability, but completely abrogated RA-induced enhanced migration. Collectively, our results indicate that RA could be a major regulator of Schwann cell migration after nerve injury, thus offering a new insight into peripheral nerve repair.

Keywords: Migration; NEDD9; Peripheral nerve regeneration; Protein stabilization; Retinoic acid; Schwann cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Dose-Response Relationship, Drug
  • LIM Domain Proteins
  • Microfilament Proteins
  • Mixed Function Oxygenases
  • Nerve Regeneration / drug effects*
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Protein Stability
  • RNA Interference
  • RNA, Messenger / metabolism
  • Rats
  • Schwann Cells / drug effects*
  • Schwann Cells / metabolism
  • Signal Transduction
  • Time Factors
  • Transcription, Genetic*
  • Transcriptional Activation*
  • Transfection
  • Tretinoin / pharmacology*
  • Up-Regulation


  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • LIM Domain Proteins
  • Microfilament Proteins
  • NEDD9 protein, rat
  • RNA, Messenger
  • Tretinoin
  • MICAL1 protein, human
  • Mixed Function Oxygenases