Microtubule‐associated protein 1B function during normal development, regeneration, and pathological conditions in the nervous system

Abstract

Microtubule-associated protein 1B is the first MAP to be expressed during the development of the nervous system. Several different approaches have revealed that MAP1B function is associated with microtubule and actin microfilament polymerization and dynamics. In recent years, the generation of molecular models to inactivate MAP1B function in invertebrates and mammals has sparked some controversy about the real role of MAP1B. Despite discrepancies between some studies, it is clear that MAP1B plays a principal role in the development of the nervous system. In this article, we summarize the evidence for MAP1B function in a wide variety of cellular processes implicated in the proper construction of the nervous system. We also discuss the role of MAP1B in pathological processes.

The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development

“…Consistent with the proposed function of FMRP in regulating translation in synaptic plasticity, activity-dependent production of the synaptic protein PSD95 is abrogated in the Fmr1 KO primary neuronal cultures (22). In addition, the mRNA of the microtubuleassociated protein 1B (MAP1B), a neuronal MAP playing principle roles in neurite and synapse development (23), is a predicted target of FMRP (18,19,21). Interestingly, deficiency of Drosophila Fmr1 (dFmr1) results in abnormally elevated expression of the microtubule associated protein Futsch and synaptic over growth at the neuromuscular junction (24), suggesting an evolutionarily conserved function of FMRP in synapse development, although the function of Futsch at neuromuscular junction may not be completely analogous to that of MAP1B in the mammalian brain.…”

Sustained GSK3 activity markedly facilitates nerve regeneration

“…MAP1B exists in at least two different modes of phosphorylation 41 , with mode II phosphorylation being mediated mainly by casein kinase II (refs 41,42) and occurring throughout the whole neuron. In contrast, mode I phosphorylation of MAP1B is concentrated in the distal part of the axon 43 and switches microtubules into a dynamic state by promoting tyrosination of a-tubulin 40,44 . Active GSK3 has been described to mediate this mode I phosphorylation at the two non-primed sites Serine 1,260 and Threonine 1,265 (refs 14,22,36).…”

Initiating and Growing an Axon

“…Further, growth factor-triggered inactivation of GSK-3b by PI3K signaling acts through APC to control axon elongation (Zhou et al 2004). Two other GSK-3 targets, the microtubule associated proteins (MAPs) MAP1b (Gonzalez-Billault et al 2004) and Tau (Sperber et al 1995), display reduced microtubule binding when phosphorylated by GSK-3. These results emphasize that the microtubule cytoskeleton is a major endpoint for polarity regulators.…”