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.
Highlights
Axons are the enormously long cable-like cellular processes of neurons that wire nervous systems
Improper extension of axons leads to neurodevelopmental defects, and age- or disease-related neurodegeneration usually starts in axons
XMAP215 and Eb1, a functional trio for microtubule polymerisation and organisation relevant data are within the paper and its Supporting information files
Summary
Axons are the enormously long cable-like cellular processes of neurons that wire nervous systems. Axons of 15μm diameter can be up to two meters long [1,2] They are constantly exposed to mechanical challenges, yet have to survive for up to a century; we lose ~40% of axons towards high age and far more in neurodegenerative diseases [3,4,5]. Their growth and maintenance absolutely require parallel bundles of microtubules (MTs) that run all along axons, providing the highways for life-sustaining transport and driving morphogenetic processes. The molecular mechanisms regulating MT polymerisation in axons are surprisingly little understood
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