Centrosome-dependent microtubule modifications set the conditions for axon formation

• Published in: Cell reports (Cambridge) Vol. 39; no. 3; p. 110686
• Main Authors: Meka, Durga Praveen, Kobler, Oliver, Hong, Shuai, Friedrich, Carina Meta, Wuesthoff, Souhaila, Henis, Melad, Schwanke, Birgit, Krisp, Christoph, Schmuelling, Nessa, Rueter, René, Ruecker, Tabitha, Betleja, Ewelina, Cheng, Tao, Mahjoub, Moe R., Soba, Peter, Schlüter, Hartmut, Fornasiero, Eugenio F., Calderon de Anda, Froylan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-04-2022
• Subjects: acetylated microtubules; Actin Cytoskeleton; axon formation; Axons - metabolism; centrosome; Centrosome - metabolism; Cep120; Microtubule-Associated Proteins - metabolism; microtubules; Microtubules - metabolism; neuronal polarity; Neurons - metabolism; CP: Cell biology; Cep120; neuronal polarity; microtubules; acetylated microtubules; centrosome; axon formation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110686

Microtubule (MT) modifications are critical during axon development, with stable MTs populating the axon. How these modifications are spatially coordinated is unclear. Here, via high-resolution microscopy, we show that early developing neurons have fewer somatic acetylated MTs restricted near the centrosome. At later stages, however, acetylated MTs spread out in soma and concentrate in growing axon. Live imaging in early plated neurons of the MT plus-end protein, EB3, show increased displacement and growth rate near the MTOC, suggesting local differences that might support axon selection. Moreover, F-actin disruption in early developing neurons, which show fewer somatic acetylated MTs, does not induce multiple axons, unlike later stages. Overexpression of centrosomal protein 120 (Cep120), which promotes MT acetylation/stabilization, induces multiple axons, while its knockdown downregulates proteins modulating MT dynamics and stability, hampering axon formation. Collectively, we show how centrosome-dependent MT modifications contribute to axon formation.
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•MT acetylation near the MTOC from stage 1 cells spread out to growing axons (stage 3)•MT acetylation in soma at stage 1 is significantly lower compared with stage 2 neurons•Centrosomal protein, Cep120, modulates axon formation through MT acetylation•TACC3, an MT-stabilizing protein, is enriched in the longest neurites at stages 2 and 3
Meka et al. show that Cep120-dependent microtubule acetylation, concentrated at the centrosome at stage 1, spreads from the soma into neurites at stage 2 and is eventually enriched in the longest neurite (axon) at stage 3. Other tubulin modifications (polyglutamylation, tyrosination) or α-tubulin itself did not follow the gradual distribution during symmetry breakage.