Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons

Hahn, Ines, Voelzmann, Andre, Parkin, Jill, Fulle, Judith B, Slater, Paula G, Lowery, Laura Anne, Sanchez-Soriano, Natalia and Prokop, Andreas (2021) Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons. PLOS GENETICS, 17 (7). e1009647-.

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Official URL: http://dx.doi.org/10.1371/journal.pgen.1009647

Abstract

The formation and maintenance of microtubules requires their polymerisation, but little is known about how this polymerisation is regulated in cells. Focussing on the essential microtubule bundles in axons of Drosophila and Xenopus neurons, we show that the plus-end scaffold Eb1, the polymerase XMAP215/Msps and the lattice-binder Tau co-operate interdependently to promote microtubule polymerisation and bundle organisation during axon development and maintenance. Eb1 and XMAP215/Msps promote each other's localisation at polymerising microtubule plus-ends. Tau outcompetes Eb1-binding along microtubule lattices, thus preventing depletion of Eb1 tip pools. The three factors genetically interact and show shared mutant phenotypes: reductions in axon growth, comet sizes, comet numbers and comet velocities, as well as prominent deterioration of parallel microtubule bundles into disorganised curled conformations. This microtubule curling is caused by Eb1 plus-end depletion which impairs spectraplakin-mediated guidance of extending microtubules into parallel bundles. Our demonstration that Eb1, XMAP215/Msps and Tau co-operate during the regulation of microtubule polymerisation and bundle organisation, offers new conceptual explanations for developmental and degenerative axon pathologies.

Item Type:	Article
Uncontrolled Keywords:	Neurons, Axons, Microtubules, Animals, Xenopus laevis, Drosophila melanogaster, Xenopus Proteins, Microtubule-Associated Proteins, tau Proteins, Drosophila Proteins, Polymerization
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	21 Jun 2021 08:17
Last Modified:	18 Jan 2023 22:34
DOI:	10.1371/journal.pgen.1009647
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3127143