A conceptual view at microtubule plus end dynamics in neuronal axons

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 lifesustaining 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.

Msps Governs Acentrosomal Microtubule Assembly and Reactivation of Quiescent Neural Stem Cells

“…Microtubule plus-end-out orientation in axons of neurons is important for axonal growth and transport (Voelzmann et al, 2016). What is the function of plus-end-out polarity in the primary protrusion of qNSCs?…”

Centrosome Loss Triggers a Transcriptional Program to Counter Apoptosis-Induced Oxidative Stress

“…Thus another potential transcriptional response might be upregulation of the components of the SAC, Augmin complex, or Ran pathway, which partially compensate for centrosome loss in wing discs as well as in the early embryo (HAYWARD et al 2014;POULTON et al 2014). Only two genes with microtubule or SAC connections were on the list of genes significantly upregulated by loss of both Asl and Sas-4: Tubulin binding cofactor A (CG1890) (VOELZMANN et al 2016), and Spindly, a protein essential for silencing the SAC via dynein recruitment to the kinetochore (GRIFFIS et al 2007). However, when we scanned the lists of genes upregulated by knockdown of sas4 or asl alone, a few additional genes emerged: rcd2, identified in an RNAi screen for centrosome function (DOBBELAERE et al 2008), and CP309, encoding the centrosomal protein Pericentrin-like protein (PLP) (MENNELLA et al 2012;LERIT et al 2015;RICHENS et al 2015), were upregulated in sas-4 mutants, while mad2, a key component of the spindle assembly checkpoint (MUSACCHIO 2015), ran, which has dual roles in nuclear import and in non-centrosomal microtubule nucleation (CLARKE AND ZHANG 2008), and cct5, involved in centrosomeindependent spindle assembly (MOUTINHO-PEREIRA et al 2013), were upregulated in asl mutants.…”

Randomness in microtubule dynamics: an error that requires correction or an inherent plasticity required for normal cellular function?

“…These kinks initiate the dynamic instability of MTs by recruiting proteins responsible for depolymerization (Sekulic et al, 2016). MTs interaction with diverse proteins regulating their dynamics, including KIF2C, KIF2A, EB1-3, TACC3, and others (Daire and Pous, 2011;van de Willige et al, 2016;Voelzmann et al, 2016;D'Angelo et al, 2017;Nehlig et al, 2017;Maurya et al, 2019).…”