Non-Muscle Myosin II in Axonal Cell Biology: From the Growth Cone to the Axon Initial Segment

Costa, Ana Rita; Sousa, Mónica Mendes

doi:10.3390/cells9091961

Cited by 29 publications

(26 citation statements)

References 120 publications

(217 reference statements)

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“…The majority of myosin dimers may thus crosslink neighboring rings, a finding confirmed at the ultrastructural level by the localization of pMLC and myosin rods using immunogold PREM and correlative SMLM/PREM [21 ]. How such crosslinking myosins -or a minor population of within-ring associated myosins -can pull along the braided filaments that form rings to generate both radial and axial contractility remains to be clarified [63,64].…”

Section: Cellular Functions Of the Mpsmentioning

confidence: 99%

Putting the axonal periodic scaffold in order

Leterrier

2021

Current Opinion in Neurobiology

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Neurons rely on a unique organization of their cytoskeleton to build, maintain and transform their extraordinarily intricate shapes. After decades of research on the neuronal cytoskeleton, it is exciting that novel assemblies are still discovered thanks to progress in cellular imaging methods. Indeed, super-resolution microscopy has revealed that axons are lined with a periodic scaffold of actin rings, spaced every 190 nm by spectrins. Determining the architecture, composition, dynamics, and functions of this membraneassociated periodic scaffold is a current conceptual and technical challenge, as well as a very active area of research. This short review aims at summarizing the latest research on the axonal periodic scaffold, highlighting recent progress and open questions.

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Section: Cellular Functions Of the Mpsmentioning

confidence: 99%

Putting the axonal periodic scaffold in order

Leterrier

2021

Current Opinion in Neurobiology

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“…NPCs represent an 'adult' or more precisely a tissue-speci c stem cell population, in which regulatory mechanism can be different from that seen in mature neurons. In addition, as previous studied made it clear, speci c cellular localization of kinases in either the RhoA-or the JNK-dependent pathway is crucial for the particular cellular functions (25,54). It is also noteworthy that we focused only on the initialization, the rst 6 hours of neurite generation.…”

Section: Discussionmentioning

confidence: 95%

“…At the tip of these projections, actin dynamics, which is driven by numerous factors, has a crucial role. One of these factors is the non-muscle myosin II, which is an ATPdriven molecular motor protein responsible for the retrograde actin ow (recently reviewed in (25)). Blebbistatin (BS) is a well-characterized, selective and potent inhibitor of NMII (26), which blocks myosin heads in a low a nity state for actin, thus preventing formation of actomyosin complexes (27,28).…”

mentioning

confidence: 99%

Pharmacological Modulation of Neurite Outgrowth in Human Neural Progenitor Cells by Inhibiting Non-Muscle Myosin II

Lilienberg

Hegyi

Szabó

et al. 2021

Preprint

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Studies on neural development and neuronal regeneration are mainly based on animal models. The establishment of pluripotent stem cell technology, however, opened new perspectives for better understanding these processes in humans by providing unlimited cell source for hard-to-obtain human tissues. Here, we aimed at identifying the molecular factors that confine and modulate an early step of neural regeneration, the formation of neurites in human neural progenitor cells (NPCs). eGFP was stably expressed in NPCs differentiated from human embryonic and induced pluripotent stem cell lines, and the neurite outgrowth was investigated under permissive and restrictive conditions using a high-content screening system. We found that the non-muscle myosin II (NMII) inhibitor blebbistatin and its novel, non-toxic derivatives initiate extensive neurite outgrowth in human NPCs. We observed that the extracellular matrix components greatly influence the rate of neurite formation, but NMII inhibitors are able to override the inhibitory effect of the restrictive environment. Similar, non-additive stimulatory effect on neurite generation was detected by the inhibition of ROCK1 kinase, the upstream regulator of NMII, whereas inhibition of JNKs had negligible effect, suggesting that ROCK1 signal is dominantly manifested by the actomyosin activity. In addition to providing a reliable cell-based in vitro model for identifying intrinsic mechanisms and environmental factors responsible for impeded axonal regeneration in humans, our results demonstrate that NMII and ROCK1 are important pharmacological targets for the augmentation of neural regeneration at the progenitor level, and may open novel perspectives in to development of more effective pharmacological and cell therapies for various neurodegenerative disorders.

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“…The NM-II may exist in multiple forms, including the unipolar NM-II, bipolar NM-II filaments or stacks, which could help bridge adjacent actin rings [7] or cross-link actin fibres within the same ring. [16,78] These NM-II molecules may also cross-link the actin cortex to actin rings to generate interlinked radial and axial tension in axons. Such a submembrane actomyosin structure may further be anchored to other cytoskeletal and PM to further fortify the long extending axon.…”

Section: Actomyosin: Force Generator Underlying Both Radial and Axial Contractilitymentioning

confidence: 99%

“…Among all three NM-II isoforms (NM-IIA, B, and C) expressed in the brain, NM-IIB is the most brain enriched one [116] and is associated with many neurological dysfunctions. [78,117] Particularly, NM-IIB expression is high in axon shafts of mature neurons, with both the myosin head and rod domains periodically distributed. But only the head domains show significant overlap with the periodic actin rings.…”

Section: Possible Roles Of Nm-ii In Axon Degenerationmentioning

confidence: 99%

The axonal radial contractility: Structural basis underlying a new form of neural plasticity

et al. 2021

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Axons are the longest cellular structure reaching over a meter in the case of human motor axons. They have a relatively small diameter and contain several cytoskeletal elements that mediate both material and information exchange within neurons.Recently, a novel type of axonal plasticity, termed axonal radial contractility, has been unveiled. It is represented by dynamic and transient diameter changes of the axon shaft to accommodate the passages of large organelles. Mechanisms underpinning this plasticity are not fully understood. Here, we first summarised recent evidence of the functional relevance for axon radial contractility, then discussed the underlying structural basis, reviewing nanoscopic evidence of the subtle changes. Two models are proposed to explain how actomyosin rings are organised. Possible roles of non-muscle myosin II (NM-II) in axon degeneration are discussed. Finally, we discuss the concept of periodic functional nanodomains, which could sense extracellular cues and coordinate the axonal responses. Also see the video abstract here: https://youtu.be/ojCnrJ8RCRc

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Non-Muscle Myosin II in Axonal Cell Biology: From the Growth Cone to the Axon Initial Segment

Cited by 29 publications

References 120 publications

Putting the axonal periodic scaffold in order

Putting the axonal periodic scaffold in order

Pharmacological Modulation of Neurite Outgrowth in Human Neural Progenitor Cells by Inhibiting Non-Muscle Myosin II

The axonal radial contractility: Structural basis underlying a new form of neural plasticity

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