1. Centrosome-dependent microtubule modifications set the conditions for axon formation
- Author
-
Durga Praveen Meka, Oliver Kobler, Shuai Hong, Carina Meta Friedrich, Souhaila Wuesthoff, Melad Henis, Birgit Schwanke, Christoph Krisp, Nessa Schmuelling, René Rueter, Tabitha Ruecker, Ewelina Betleja, Tao Cheng, Moe R. Mahjoub, Peter Soba, Hartmut Schlüter, Eugenio F. Fornasiero, and Froylan Calderon de Anda
- Subjects
Centrosome ,Neurons ,Actin Cytoskeleton ,nervous system ,microtubules ,Cell biology ,acetylated microtubules ,neuronal polarity ,axon formation ,centrosome ,Cep120 ,Microtubule-Associated Proteins ,Microtubules ,General Biochemistry, Genetics and Molecular Biology ,Axons - Abstract
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.
- Published
- 2021