Centrosome-dependent microtubule modifications set the conditions for axon formation

  • Cell Rep. 2022 Apr 19;39(3):110686. doi: 10.1016/j.celrep.2022.110686.
Durga Praveen Meka  1 ,  Oliver Kobler  2 ,  Shuai Hong  1 ,  Carina Meta Friedrich  1 ,  Souhaila Wuesthoff  1 ,  Melad Henis  3 ,  Birgit Schwanke  1 ,  Christoph Krisp  4 ,  Nessa Schmuelling  1 ,  René Rueter  1 ,  Tabitha Ruecker  1 ,  Ewelina Betleja  5 ,  Tao Cheng  5 ,  Moe R Mahjoub  5 ,  Peter Soba  6 ,  Hartmut Schlüter  4 ,  Eugenio F Fornasiero  7 ,  Froylan Calderon de Anda  8
Affiliations
  • 1. Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • 2. Combinatorial Neuroimaging Core Facility, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
  • 3. Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany; Department of Anatomy and Histology, Faculty of Veterinary Medicine, New Valley University, 72511 El-Kharga, Egypt.
  • 4. Institute for Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics Group, Campus Forschung, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • 5. Department of Medicine (Nephrology Division), Washington University, St. Louis, MO 63110, USA.
  • 6. LIMES Institute, Department of Molecular Brain Physiology and Behavior, University of Bonn, 53115 Bonn, Germany; Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
  • 7. Department of Neuro- and Sensory Physiology, University Medical Center Göttingen, 37073 Göttingen, Germany.
  • 8. Institute of Developmental Neurophysiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. Electronic address: [email protected].
PMID: 35443171 DOI: 10.1016/j.celrep.2022.110686
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.

Keywords
CP: Cell biology; Cep120; acetylated microtubules; axon formation; centrosome; microtubules; neuronal polarity.
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