Nucleus-localized 21.5-kDa myelin basic protein promotes oligodendrocyte proliferation and enhances neurite outgrowth in coculture, unlike the plasma membrane-associated 18.5-kDa isoform

J Neurosci Res. 2013 Mar;91(3):349-62. doi: 10.1002/jnr.23166. Epub 2012 Nov 27.

Abstract

The classic myelin basic protein (MBP) family of central nervous system (CNS) myelin arises from transcription start site 3 of the Golli (gene of oligodendrocyte lineage) complex and comprises splice isoforms ranging in nominal molecular mass from 14 kDa to (full-length) 21.5 kDa. We have determined here a number of distinct functional differences between the major 18.5-kDa and minor 21.5-kDa isoforms of classic MBP with respect to oligodendrocyte (OLG) proliferation. We have found that, in contrast to 18.5-kDa MBP, 21.5-kDa MBP increases proliferation of early developmental immortalized N19-OLGs by elevating the levels of phosphorylated ERK1/2 and Akt1 kinases and of ribosomal protein S6. Coculture of N2a neuronal cells with N19-OLGs transfected with the 21.5-kDa isoform (or conditioned medium from), but not the 18.5-kDa isoform, caused the N2a cells to have increased neurite outgrowth and process branching complexity. These roles were dependent on subcellular localization of 21.5-kDa MBP to the nucleus and on the exon II-encoded segment, suggesting that the nuclear localization of early minor isoforms of MBP may play a crucial role in regulating and/or initiating myelin and neuronal development in the mammalian CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism*
  • Cell Nucleus / physiology
  • Cell Proliferation*
  • Coculture Techniques
  • Mice
  • Molecular Weight
  • Myelin Basic Protein / chemistry
  • Myelin Basic Protein / metabolism
  • Myelin Basic Protein / physiology*
  • Neurites / chemistry
  • Neurites / physiology*
  • Oligodendroglia / chemistry
  • Oligodendroglia / metabolism*
  • Protein Isoforms / physiology

Substances

  • Myelin Basic Protein
  • Protein Isoforms