Unrestrained growth of correctly oriented microtubules instructs axonal microtubule orientation

Jakobs MA, Zemel A, Franze K (2022)

Publication Type: Journal article

Publication year: 2022

Journal

eLife eLife Sciences Publications

Book Volume: 11

DOI: 10.7554/eLife.77608

Abstract

In many eukaryotic cells, directed molecular transport occurs along microtubules. Within neuronal axons, transport over vast distances particularly relies on uniformly oriented microtubules, whose plus-ends point towards the distal axon tip (anterogradely polymerizing, or plus-end-out). However, axonal microtubules initially have mixed orientations, and how they orient during development is not yet fully understood. Using live imaging of primary Drosophila melanogaster neurons, we found that, in the distal part of the axon, catastrophe rates of plus-end-out microtubules were significantly reduced compared to those of minus-end-out microtubules. Physical modelling revealed that plus-end-out microtubules should therefore exhibit persistent long-term growth, while growth of minus-end-out microtubules should be limited, leading to a bias in overall axonal microtubule orientation. Using chemical and physical perturbations of microtubule growth and genetic perturbations of the anti -catastrophe factor p150, which was enriched in the distal axon tip, we confirmed that the enhanced growth of plus-end-out microtubules is critical for achieving uniform microtubule orientation. Computer simulations of axon development integrating the enhanced plus-end-out microtubule growth identified here with previously suggested mechanisms, that is, dynein-based microtubule sliding and augmin-mediated templating, correctly predicted the long-term evolution of axonal microtubule orientation as found in our experiments. Our study thus leads to a holistic explanation of how axonal microtubules orient uniformly, a prerequisite for efficient long-range transport essential for neuronal functioning.

Authors with CRIS profile

Kristian Franze Lehrstuhl für Medizinische Physik und Mikrogewebetechnik

Involved external institutions

University of Cambridge GB United Kingdom (GB) Hebrew University of Jerusalem IL Israel (IL)

How to cite

APA:

Jakobs, M.A., Zemel, A., & Franze, K. (2022). Unrestrained growth of correctly oriented microtubules instructs axonal microtubule orientation. eLife, 11. https://dx.doi.org/10.7554/eLife.77608

MLA:

Jakobs, Maximilian A.H., Assaf Zemel, and Kristian Franze. "Unrestrained growth of correctly oriented microtubules instructs axonal microtubule orientation." eLife 11 (2022).

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