MTOC Organization and Competition During Neuron Differentiation

Tann, Jason Y.; Moore, Adrian W.

doi:10.1007/978-3-030-23173-6_14

Cited by 6 publications

(6 citation statements)

References 117 publications

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“…Mechanisms of MT nucleation have long been known to be independent of centrosomes [219, 220] and should therefore involve cytoplasmic assembly or non-centrosomal MTOCs (MT organising centres; [221, 222]). For example, tau was reported to form condensations on MTs in vitro [179, 180], and such condensed phases of tau could theoretically have nucleation capacity [223, 224].…”

Section: Mt Nucleation and Polymerisation As Fundamental Requirementsmentioning

confidence: 99%

The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology

et al. 2019

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Axons are the slender, cable-like, up to meter-long projections of neurons that electrically wire our brains and bodies. In spite of their challenging morphology, they usually need to be maintained for an organism's lifetime. This makes them key lesion sites in pathological processes of ageing, injury and neurodegeneration. The morphology and physiology of axons crucially depends on the parallel bundles of microtubules (MTs), running all along to serve as their structural backbones and highways for life-sustaining cargo transport and organelle dynamics. Understanding how these bundles are formed and then maintained will provide important explanations for axon biology and pathology. Currently, much is known about MTs and the proteins that bind and regulate them, but very little about how these factors functionally integrate to regulate axon biology. As an attempt to bridge between molecular mechanisms and their cellular relevance, we explain here the model of local axon homeostasis, based on our own experiments in Drosophila and published data primarily from vertebrates/mammals as well as C. elegans. The model proposes that (1) the physical forces imposed by motor protein-driven transport and dynamics in the confined axonal space, are a life-sustaining necessity, but pose a strong bias for MT bundles to become disorganised. (2) To counterbalance this risk, MT-binding and-regulating proteins of different classes work together to maintain and protect MT bundles as necessary transport highways. Loss of balance between these two fundamental processes can explain the development of axonopathies, in particular those linking to MT-regulating proteins, motors and transport defects. With this perspective in mind, we hope that more researchers incorporate MTs into their work, thus enhancing our chances of deciphering the complex regulatory networks that underpin axon biology and pathology.

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Section: Mt Nucleation and Polymerisation As Fundamental Requirementsmentioning

confidence: 99%

The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology

et al. 2019

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“…75 Far less is known about the biology of protein aggregates in mammalian cells, especially in compartmentalized, postmitotic or slowly dividing cells such as neurons and glia, especially in the context of the adult brain. Given that the MTOC in neurons is repurposed for axon and dendrite differentiation 77 and no longer perinuclear, how the compartments might be segregated is unclear. Although the organization might differ in terminally differentiated cells, the likelihood that cargoes are sorted is high.…”

Section: Are Aggregates Protective or Pathogenic? Yes No And Maybementioning

confidence: 99%

Dissolving the Complex Role Aggregation Plays in Neurodegenerative Disease

Croce

Yamamoto

2021

Movement Disorders

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Prominent neuropathological hallmarks of many adult‐onset neurodegenerative diseases include the deposition and accumulation of misfolded proteins or conformers; however, their role in pathogenesis has remained unclear. This is in part due to the deceptive simplicity of the question and our limited understanding of how protein homeostasis is maintained in the compartmentalized cells of the central nervous system, especially in the context of the adult brain. Building on studies from simple cell‐based systems and invertebrate animals, we recently identified a protein central to the specific and selective turnover of aggregated proteins in the adult brain, the autophagy‐linked FYVE protein (Alfy)/Wdfy3. Depletion of Alfy levels in a mouse model of Huntington's disease showed that it accelerated the accumulation of the aggregated mutant huntingtin protein, as well as the onset of behavioral deficits. Although the motor dysfunction was accelerated in the model, this was in the absence of increasing overt cell loss, implicating protein aggregates as a modifier of circuit dysfunction rather than driving degeneration per se. We discuss these findings in the context of what is known about protein accumulation and how we can use proteins such as Alfy to determine if protein accumulation is a shared pathogenic event across different adult‐onset diseases. © 2021 International Parkinson and Movement Disorder Society

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“…MTOCs compete amongst themselves for common resources within a cell; for example, in Drosophila syncytial embryos, blocking Augmin-dependent nucleation in spindles increases centrosome activity, while reducing centrosomal nucleation activity increases nucleation in the spindle (Hayward et al, 2014). A tug-of-war like competition for a restricted population of γ-TuRC recruitment factors is the likely mechanism [further discussed by (Tann and Moore, 2019)]. Because of this potential for tug-of-war competition between MTOCs, one way to shape the microtubule network during neuron differentiation is by differential regulation of γ-TuRC-TPs levels or activity, and an example of this is neuron type-specific control of Cnn in Drosophila da neurons (Yalgin et al, 2015).…”

Section: Organization and Competition Between Molecular Machineries Omentioning

confidence: 99%

Distinct Microtubule Organizing Center Mechanisms Combine to Generate Neuron Polarity and Arbor Complexity

Wilkes

Moore

2020

Front. Cell. Neurosci.

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Dendrite and axon arbor wiring patterns determine the connectivity and computational characteristics of a neuron. The identities of these dendrite and axon arbors are created by differential polarization of their microtubule arrays, and their complexity and pattern are generated by the extension and organization of these arrays. We describe how several molecularly distinct microtubule organizing center (MTOC) mechanisms function during neuron differentiation to generate and arrange dendrite and axon microtubules. The temporal and spatial organization of these MTOCs generates, patterns, and diversifies arbor wiring.

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MTOC Organization and Competition During Neuron Differentiation

Cited by 6 publications

References 117 publications

The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology

The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology

Dissolving the Complex Role Aggregation Plays in Neurodegenerative Disease

Distinct Microtubule Organizing Center Mechanisms Combine to Generate Neuron Polarity and Arbor Complexity

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