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

Stephen R. Tymanskyj, Shen Lin, Phillip R. Gordon-Weeks

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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 3 beta (GSK-3 beta) at a site that requires prior phosphorylation by another kinase four amino acid residues downstream of the GSK-3 beta site, a so-called primed site, and at non-primed sites that have no such requirement. In developing mammalian neurons, MAP1B phosphorylated by GSK-3 beta at primed and non-primed sites is distributed in spatially distinct patterns. Non-primed GSK-3 beta-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-3 beta-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-3 beta 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-3 beta primed and non-primed sites on MAP1B. This revealed a remarkable evolutionary conservation of the distribution of primed and non-primed GSK-3 beta-phosphorylated MAP1B sites in developing vertebrate neurons. By analysing amino acid sequences of MAP1B we found that non-primed GSK-3 beta sites are more highly conserved than primed sites throughout the vertebrates, suggesting that the latter evolved later. Finally, distinct distribution patterns of GSK-3 beta 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.
Original languageEnglish
Pages (from-to)692 - 704
Number of pages13
JournalJournal of Anatomy
Volume216
Issue number6
DOIs
Publication statusPublished - Jun 2010

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