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



Hahn, Ines ORCID: 0000-0001-7703-8160, Voelzmann, Andre, Parkin, Jill, Fuelle, Judith, Slater, Paula G, Lowery, Laura A, Sanchez-Soriano, Natalia and Prokop, Andreas
Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons.

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Abstract

<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>Drosophila</jats:italic> and <jats:italic>Xenopus</jats:italic> 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 size, comet number and comet velocity, 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 and how to treat them.</jats:p><jats:sec><jats:title>Summary statement</jats:title><jats:p>Eb1, XMAP215 and tau co-operate interdependently in axons to promote the polymerisation of microtubules and their organisation into the parallel bundles required for axonal transport.</jats:p></jats:sec>

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 21 Jan 2021 15:14
Last Modified: 02 May 2022 18:12
DOI: 10.1101/2020.08.19.257808
URI: https://livrepository.liverpool.ac.uk/id/eprint/3114413