Evolution of the spatial distribution of MAP1B phosphorylation sites in vertebrate neurons

J Anat. 2010 Jun;216(6):692-704. doi: 10.1111/j.1469-7580.2010.01228.x. Epub 2010 Apr 9.

Abstract

The microtubule-associated protein MAP1B has important roles in neural development, particularly in migrating and differentiating neurons. MAP1B is phosphorylated by glycogen synthase kinase 3beta (GSK-3beta) at a site that requires prior phosphorylation by another kinase four amino acid residues downstream of the GSK-3beta site, a so-called primed site, and at non-primed sites that have no such requirement. In developing mammalian neurons, MAP1B phosphorylated by GSK-3beta at primed and non-primed sites is distributed in spatially distinct patterns. Non-primed GSK-3beta-phosphorylated MAP1B sites are only expressed in axons and are present in the form of a gradient that is highest distally, towards the growth cone. In contrast, primed GSK-3beta-phosphorylated MAP1B sites are present throughout the neuron including the somato-dendritic compartment and uniformly throughout the axon. To examine the function of these two sites, we explored the evolutionary conservation of the spatial distribution of GSK-3beta primed and non-primed sites on MAP1B in vertebrate neurons. We immunostained spinal cord sections from embryonic or newly hatched representatives of all of the main vertebrate groups using phospho-specific antibodies to GSK-3beta primed and non-primed sites on MAP1B. This revealed a remarkable evolutionary conservation of the distribution of primed and non-primed GSK-3beta-phosphorylated MAP1B sites in developing vertebrate neurons. By analysing amino acid sequences of MAP1B we found that non-primed GSK-3beta sites are more highly conserved than primed sites throughout the vertebrates, suggesting that the latter evolved later. Finally, distinct distribution patterns of GSK-3beta primed and non-primed sites on MAP1B were preserved in cultured rat embryonic cortical neurons, opening up the possibility of studying the two sites in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution*
  • Glycogen Synthase Kinase 3 / analysis
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Phosphorylation
  • Rats
  • Snakes
  • Xenopus laevis
  • Zebrafish

Substances

  • Microtubule-Associated Proteins
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Glycogen Synthase Kinase 3