The GSK3-MAP1B pathway controls neurite branching and microtubule dynamics

Monia Barnat , Marie-Noelle Benassy , Laetitia Vincensini , Sylvia Soares , Coralie Fassier (1) , Friedrich Propst , Annie Andrieux , Ysander Von Boxberg , Fatiha Nothias

1 NPS-08 - Développement et dégénérescence des neurones moteurs spinaux = Development and Degeneration of Spinal Motor neurons in the zebrafish

The microtubule-associated protein MAP1B plays a key role in axon regeneration. We investigated the role of GSK3-mediated MAP1B phosphorylation in local fine-tuning of neurite branching and the underlying microtubule (MT) dynamics. In wildtype adult dorsal root ganglia (DRG) neurons, MAP1B phosphorylation is locally reduced at branching points, and branching dynamics from growth cones and distal neurite shafts is increased upon GSK3 inhibition. While map1b-/- neurites, that display increased branching, are not affected by GSK3 inhibition, transfection of map1b-/- neurons with full-length map1b-cDNA restores the wildtype branching phenotype, demonstrating that MAP1B is a key effector downstream of GSK3. Experiments in mutant mice lacking tyrosinated MTs indicate a preferential association of phospho-MAP1B with tyrosinated MTs. Interestingly, inhibition of GSK3-mediated MAP1B phosphorylation in map1b-cDNA-transfected fibroblasts protects both tyrosinated and acetylated MTs from nocodazole-induced depolymerization, while detyrosinated MTs are less abundant in the presence of MAP1B. Our data thus provide new insight into the molecular link between GSK3, MAP1B, neurite branching and MT stability regulation. We suggest that, at branching points, MAP1B undergoes a fine regulation of both its phosphorylation and sub-cellular amounts, in order to modulate the local balance between acetylated, detyrosinated, and tyrosinated microtubule pools.

Mots clés: DRG neurons; Cell neurobiology; Cytoskeleton; Microtubule-associated protein 1B; Neurite outgrowth; Regeneration; GSK signaling; Acetylated microtubules; Detyrosinated microtubules; Tyrosinated microtubules; Nocodazole; SB216763 GSK inhibitor; COS-7 cells; MAP1B-knockout mice; Tubulin-tyrosine ligase (TTL)-deficient mice

Domaines: Neurosciences

Monia Barnat, Marie-Noelle Benassy, Laetitia Vincensini, Sylvia Soares, Coralie Fassier, et al.. The GSK3-MAP1B pathway controls neurite branching and microtubule dynamics. Molecular and Cellular Neuroscience, 2016, 72, pp.9-21. ⟨10.1016/j.mcn.2016.01.001⟩. ⟨hal-01542347⟩