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Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex

Qu, Yue; Hahn, Ines; Lees, Meredith; Parkin, Jill; Voelzmann, Andr�; Dorey, Karel; Rathbone, Alex; Friel, Claire T; Allan, Victoria J; Okenve-Ramos, Pilar; Sanchez-Soriano, Natalia; Prokop, Andreas

Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex Thumbnail


Authors

Yue Qu

Ines Hahn

Meredith Lees

Jill Parkin

Andr� Voelzmann

Karel Dorey

Alex Rathbone

Victoria J Allan

Pilar Okenve-Ramos

Natalia Sanchez-Soriano

Andreas Prokop



Abstract

© 2019, Qu et al. Cortical collapse factors affect microtubule (MT) dynamics at the plasma membrane. They play important roles in neurons, as suggested by inhibition of axon growth and regeneration through the ARF activator Efa6 in C. elegans, and by neurodevelopmental disorders linked to the mammalian kinesin Kif21A. How cortical collapse factors influence axon growth is little understood. Here we studied them, focussing on the function of Drosophila Efa6 in experimentally and genetically amenable fly neurons. First, we show that Drosophila Efa6 can inhibit MTs directly without interacting molecules via an N-terminal 18 amino acid motif (MT elimination domain/MTED) that binds tubulin and inhibits microtubule growth in vitro and cells. If N-terminal MTED-containing fragments are in the cytoplasm they abolish entire microtubule networks of mouse fibroblasts and whole axons of fly neurons. Full-length Efa6 is membrane-attached, hence primarily blocks MTs in the periphery of fibroblasts, and explorative MTs that have left axonal bundles in neurons. Accordingly, loss of Efa6 causes an increase of explorative MTs: in growth cones they enhance axon growth, in axon shafts they cause excessive branching, as well as atrophy through perturbations of MT bundles. Efa6 over-expression causes the opposite phenotypes. Taken together, our work conceptually links molecular and sub-cellular functions of cortical collapse factors to axon growth regulation and reveals new roles in axon branching and in the prevention of axonal atrophy. Furthermore, the MTED delivers a promising tool that can be used to inhibit MTs in a compartmentalised fashion when fusing it to specifically localising protein domains.

Citation

Qu, Y., Hahn, I., Lees, M., Parkin, J., Voelzmann, A., Dorey, K., …Prokop, A. (2019). Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex. eLife, 8, Article e50319. https://doi.org/10.7554/elife.50319

Journal Article Type Article
Acceptance Date Nov 6, 2019
Online Publication Date Nov 13, 2019
Publication Date Nov 27, 2019
Deposit Date Dec 9, 2019
Publicly Available Date Mar 28, 2024
Journal eLife
Electronic ISSN 2050-084X
Publisher eLife Sciences Publications
Peer Reviewed Peer Reviewed
Volume 8
Article Number e50319
DOI https://doi.org/10.7554/elife.50319
Keywords General Biochemistry, Genetics and Molecular Biology; General Immunology and Microbiology; General Neuroscience; General Medicine
Public URL https://nottingham-repository.worktribe.com/output/3515983

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