NMDA receptor activation stimulates transcription-independent rapid wnt5a protein synthesis via the MAPK signaling pathway

Mol Brain. 2012 Jan 4;5:1. doi: 10.1186/1756-6606-5-1.

Abstract

Wnt proteins are emerging key regulators of the plasticity and functions of adult brains. However, the mechanisms by which the expression of Wnt proteins is regulated in neurons are unclear. Using cortical primary cultures, we show here that activation of NMDA receptors (NMDARs) induces rapid Wnt5a protein synthesis and secretion. This NMDAR-regulated Wnt5a synthesis does not require transcription and is a result of activity-dependent translation. We also show that NMDAR-regulated Wnt5a translation depends on MAPK signaling but not mTOR signaling. Our findings suggest that the synaptic activity of CNS neurons activates NMDARs, which in turn stimulate translation from stored Wnt5a mRNA via the MAPK signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Protein Biosynthesis*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription, Genetic*
  • Wnt Proteins / biosynthesis*
  • Wnt-5a Protein

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • TOR Serine-Threonine Kinases