RT Journal Article
SR Electronic
T1 Tau, XMAP215/Msps and Eb1 jointly regulate microtubule polymerisation and bundle formation in axons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.19.257808
DO 10.1101/2020.08.19.257808
A1 Hahn, Ines
A1 Voelzmann, Andre
A1 Parkin, Jill
A1 Fuelle, Judith
A1 Slater, Paula G
A1 Lowery, Laura A
A1 Sanchez-Soriano, Natalia
A1 Prokop, Andreas
YR 2020
UL http://biorxiv.org/content/early/2020/08/20/2020.08.19.257808.abstract
AB Axons are the enormously long cable-like cellular processes of neurons that wire nervous systems and have to survive for up to a century in humans. We lose ~40% of axons towards high age and far more in neurodegenerative diseases. Sustaining axons requires axonal transport and dynamic morphogenetic changes, both crucially dependent on bundles of microtubules that run all along axons. How polymerisation is regulated to form, repair and replace microtubules in these bundles during axon development and maintenance is virtually unknown. Here, we show in axons of Drosophila and Xenopus neurons alike that Eb1, XMAP215/Msps and Tau are key players which operate as one functional unit to promote microtubule polymerisation. Eb1 and XMAP215/Msps are interdependent core factors at the microtubule tip, whereas Tau outcompetes Eb1 binding at microtubule lattices, thus preventing its pool depletion at polymerising plus ends. In agreement with their closely interwoven functions, the three factors show the same combination of axonal loss-of-function mutant phenotypes including: (1) reduced microtubule polymerisation dynamics and shorter axon growth, indicating their importance for upholding microtubule mass in axons; (2) prominent deterioration of parallel microtubule bundles into disorganised curled conformations, indicating their key roles in promoting essential axonal architecture. We show the latter to occur through Eb1- and spectraplakin-dependent guidance of extending microtubules. We conclude that Eb1, XMAP215/Msps and Tau jointly promote microtubule polymerisation, important to regulate the quantity and bundled organisation of microtubules and offering new ways to think about developmental and degenerative axon pathologies and how to treat them.Summary statement Eb1, XMAP215 and tau operate as a functional unit in axons to promote the polymerisation of microtubules and their organisation into the parallel bundles essential for axonal transport.Competing Interest StatementThe authors have declared no competing interest.