Abstract
Axons are the cable-like protrusions of neurons which wire up the nervous system. Polar bundles of microtubules (MTs) constitute their structural backbones and are highways for life-sustaining transport between proximal cell bodies and distal synapses. Any morphogenetic changes of axons during development, plastic rearrangement, regeneration or degeneration depend on dynamic changes of these MT bundles. A key mechanism for implementing such changes is the coordinated polymerisation and depolymerisation at the plus ends of MTs within these bundles. To gain an understanding of how such regulation can be achieved at the cellular level, we provide here an integrated overview of the extensive knowledge we have about the molecular mechanisms regulating MT de/polymerisation. We first summarise insights gained from work in vitro, then describe the machinery which supplies the essential tubulin building blocks, the protein complexes associating with MT plus ends, and MT shaft-based mechanisms that influence plus end dynamics. We briefly summarise the contribution of MT plus end dynamics to important cellular functions in axons, and conclude by discussing the challenges and potential strategies of integrating the existing molecular knowledge into conceptual understanding at the level of axons.
Highlights
Axons are the slender, up-to-a-metre long processes of neurons which form the cables that wire the nervous system
It has been proposed from studies in developing vertebrate and Drosophila neurons that the MT mass generated in the axonal shaft gradually shifts anterogradely (Miller and Sheetz, 2006; Roossien et al, 2013)
Before delving into the molecular complexity observed at the cellular level, it is important to provide a brief overview of our knowledge about the physical and biochemical properties of tubulin and MT dynamics gained from 5 decades of intense in vitro studies
Summary
Up-to-a-metre long processes of neurons which form the cables that wire the nervous system. In vivo, these dynamics are not left to chance but are controlled by different classes of MT binding proteins (MTBPs) and the proteins they recruit and associate with Such MT binding and associating proteins regulate polymerisation, severing, depolymerisation, stability, transport and force production, as well as cross-linkage and interaction with other organelles or cell structures (Penazzi et al, 2016; Prokop et al, 2013). Many of these MTBPs and associated proteins have acknowledged links to brain disorders or other human diseases (Prokop et al, 2013). We provide a conceptual overview of the sub-machinery (or submachineries) that governs the polymerisation and depolymerisation of MTs in axons
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