Neuritin 1 promotes neuronal migration

Brain Struct Funct. 2014 Jan;219(1):105-18. doi: 10.1007/s00429-012-0487-1. Epub 2012 Dec 5.

Abstract

Neuritin 1 (Nrn1 or cpg15-1) is an activity-dependent protein involved in synaptic plasticity during brain development, a process that relies upon neuronal migration. By analyzing Nrn1 expression, we found that it is highly expressed in a mouse model of migrating immortalized neurons (GN11 cells), but not in a mouse model of non-migrating neurons (GT1-7 cells). We thus hypothesized that Nrn1 might control neuronal migration. By using complementary assays, as Boyden's microchemotaxis, scratch-wounding and live cell imaging, we found that GN11 cell migration is enhanced when Nrn1 is overexpressed and decreased when Nrn1 is silenced. The effects of Nrn1 in promoting neuronal migration have been then confirmed ex vivo, on rat cortical interneurons, by Boyden chamber assays and focal electroporation of acute embryonic brain slices. Furthermore, we found that Nrn1 level modulation affects GN11 cell morphology. The process is also paralleled by Nrn1-induced α-tubulin post-translational modifications, a well-recognized marker of microtubule stability. Altogether, the data demonstrate a novel function of Nrn1 in promoting migration of neuronal cells and indicate that Nrn1 levels impact on microtubule stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Cell Differentiation
  • Cell Movement / physiology*
  • Cells, Cultured
  • Down-Regulation / physiology
  • Embryo, Mammalian
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / physiology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Median Eminence / cytology
  • Mice
  • Neurons / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / physiology*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tissue Culture Techniques
  • Tubulin / metabolism
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Substances

  • GPI-Linked Proteins
  • Neuropeptides
  • Nrn1 protein, rat
  • Tubulin
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins