A conceptual view at microtubule plus end dynamics in neuronal axons

Abstract

HighlightsAxons are the cable-like extensions of neurons which wire the brain.Axon formation and maintenance requires ordered microtubule (MT) bundles.We discuss the mechanisms that regulate the de/polymerisation of axonal MTs.We discuss the model of local homeostasis to explain the maintenance of MT bundles.

Periodic actin structures in neuronal axons are required to maintain microtubules

“…To analyze relations between PMS and MTs in a quantifiable manner, we used a further phenotype of shot 3 mutant neurons, consisting of varicose regions of axons formed by disorganized MTs that are not arranged into bundles but curl up and criss-cross each other (Figure 8A; Sánchez-Soriano et al , 2009; Voelzmann et al , 2016a). Measurements of these areas are easy to perform and statistically robust across large neuron populations and we express them as the MT disorganization index (MDI; Materials and Methods ).…”

“…Active maintenance, including constant polymerization and disassembly of MTs, is required to prevent decay through wear and tear, but hardly anything is known about these mechanisms (Voelzmann et al , 2016a). Here we report that axonal actin and the spectraplakin protein Shot have independent, complementary roles in regulating and maintaining MT polymerization in growing and mature axons, and we show that the combined absence of these mechanisms induces severe axon loss.…”

“…Axon maintenance requires continued MT polymerization and disassembly to prevent senescence of MT bundles in axons (Voelzmann et al , 2016a). In this scenario, the roles of PMS/cortical actin in sustaining MT polymerization proposed here offer conceptually new potential explanations for brain disorders linked to gene mutations of cortical actin regulators: adducin (ADD3) is linked to human cerebral palsy (Kruer et al , 2013), β-spectrin to spinocerebellar ataxia (SPTBN2; Online Mendelian Inheritance in Man [OMIM] ID: 600224, 615386), ankyrin to mental retardation (ANK3; OMIM ID: 615493), and actin to Baraitser–Winter syndrome and dystonia with neurodegenerative traits (ACTB7; OMIM ID: 243310, 607371).…”

“…Similarly, spectraplakins as the second important promoters of MT polymerization link to the neurodegenerative disorder type IV hereditary sensory and autonomic neuropathy (OMIM ID: 614653). Although a number of mechanisms have been proposed (Alves-Silva et al , 2012; Ferrier et al , 2013; Voelzmann et al , 2016a), weakening of the MT polymerization machinery might be a further mechanism underlying this disorder.…”

“…The challenge will be to find the mechanisms linking cortical actin networks to MT polymerization. This will not be a trivial task, given that MT polymerization is coordinated by a complex machinery that involves the regulation of tubulin supply, a large number of proteins associating with MT plus ends, and shaft-based mechanisms (Voelzmann et al , 2016a). …”