FMRP-Mediated Axonal Delivery of miR-181d Regulates Axon Elongation by Locally Targeting Map1b and Calm1

Cell Rep. 2015 Dec 29;13(12):2794-807. doi: 10.1016/j.celrep.2015.11.057. Epub 2015 Dec 17.

Abstract

Subcellular targeting and local translation of mRNAs are critical for axon development. However, the precise local control of mRNA translation requires investigation. We report that the Fmr1-encoded protein, FMRP-mediated axonal delivery of miR-181d negatively regulates axon elongation by locally targeting the transcripts of MAP1B (Map1b) and calmodulin (Calm1) in primary sensory neurons. miR-181d affected the local synthesis of MAP1B and calmodulin in axons. FMRP was associated with miR-181d, Map1b, and Calm1. Both FMRP deficiency in Fmr1(I304N) mice and Fmr1 knockdown impeded the axonal delivery of miR-181d, Map1b, and Calm1 and reduced the protein levels of MAP1B and calmodulin in axons. Furthermore, nerve growth factor (NGF) induced Map1b and Calm1 release from FMRP and miR-181d-repressing granules, thereby promoting axon elongation. Both miR-181d overexpression and FMRP knockdown impaired NGF-induced axon elongation. Our study reveals a mechanism for the local regulation of translation by miR-181d and FMRP during axon development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Calmodulin / genetics*
  • Calmodulin / metabolism
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Mental Retardation Protein / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Transfection

Substances

  • Calm1 protein, mouse
  • Calmodulin
  • Fmr1 protein, mouse
  • MIRN191 microRNA, mouse
  • MicroRNAs
  • Microtubule-Associated Proteins
  • microtubule-associated protein 1B
  • Fragile X Mental Retardation Protein