Actin Waves: Origin of Cell Polarization and Migration?

Inagaki, Naoyuki; Katsuno, Hiroko

doi:10.1016/j.tcb.2017.02.003

Cited by 127 publications

(117 citation statements)

References 76 publications

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“…The value of the activator diffusion coefficient in our model suggests the involvement of regulators diffusing on the membrane. Several candidates, to be resolved in future studies, can play a role upstream of actin polymerization (Inagaki & Katsuno, ), such as SCAR/WAVE (Millius, Watanabe, & Weiner, ), small GTPases (Machacek & Danuser, ), and PIP3 (Taniguchi et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…However, the effective diffusion calculated by random branching may be too slow to account for the activator's diffusion coefficient in our model (Ryan, Petroccia, et al, 2012). Other actin polymerization regulators such as VASP (Barnhart, Allard, et al, 2017) polymerization (Inagaki & Katsuno, 2017), such as SCAR/WAVE (Millius, Watanabe, & Weiner, 2012), small GTPases (Machacek & Danuser, 2006), and PIP3 (Taniguchi et al, 2013).…”

Section: Response Of Leading Edge To Membrane Perturbationmentioning

confidence: 95%

“…In a previous study using XTC cells (Figure a), which are cells with flat lamellipodia, the waves of protrusion were accompanied by waves of LifeAct‐labeled F‐actin accumulation along the lamellipodium (Ryan, Petroccia, et al, ) (Figure b–d). This phenomenon belongs to the general class of cellular actin waves (Inagaki & Katsuno, ). The XTC cells' leading edge had a period of 130–200 s. In all three cells depicted in Figure b the cell extends 1–2 μm during a cycle of protrusion and retraction.…”

Section: Introductionmentioning

confidence: 99%

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Cell protrusion and retraction driven by fluctuations in actin polymerization: A two‐dimensional model

et al. 2017

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Animal cells that spread onto a surface often rely on actin-rich lamellipodial extensions to execute protrusion. Many cell types recently adhered on a two-dimensional substrate exhibit protrusion and retraction of their lamellipodia, even though the cell is not translating. Traveling waves of protrusion have also been observed, similar to those observed in crawling cells. These regular patterns of protrusion and retraction allow quantitative analysis for comparison to mathematical models. The periodic fluctuations in leading edge position of XTC cells have been linked to excitable actin dynamics using a one-dimensional model of actin dynamics, as a function of arc-length along the cell. In this work we extend this earlier model of actin dynamics into two dimensions (along the arc-length and radial directions of the cell) and include a model membrane that protrudes and retracts in response to the changing number of free barbed ends of actin filaments near the membrane. We show that if the polymerization rate at the barbed ends changes in response to changes in their local concentration at the leading edge and/or the opposing force from the cell membrane, the model can reproduce the patterns of membrane protrusion and retraction seen in experiment. We investigate both Brownian ratchet and switch-like force-velocity relationships between the membrane load forces and actin polymerization rate. The switch-like polymerization dynamics recover the observed patterns of protrusion and retraction as well as the fluctuations in F-actin concentration profiles. The model generates predictions for the behavior of cells after local membrane tension perturbations.

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Section: Discussionmentioning

confidence: 99%

Section: Response Of Leading Edge To Membrane Perturbationmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Cell protrusion and retraction driven by fluctuations in actin polymerization: A two‐dimensional model

et al. 2017

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“…Second, MT nucleation frequency has been observed to increase immediately behind actin waves (Winans et al, 2016). Given that actin waves are responsible for the anterograde transport of a variety of biological molecules (Inagaki and Katsuno, 2017), we hypothesize that they are also in charge of moving RanGTP molecules towards neurite tips. Perhaps the elevated MT nucleation frequency observed by Winan and colleagues is caused by RanGTP moving with actin waves, causing ncMT formation in its wake.…”

Section: Actin Waves Transport Gtp-bound Ran Towards the Neurite Tipmentioning

confidence: 89%

“…Given that the actin wave has been documented to transport various cellular cargoes in neurons (Inagaki and Katsuno, 2017) and that neurite tip enriched RanGTP depends on actin-based structures, the actin wave appears as an attractive candidate for the localization of RanGTP. To determine whether actin waves are the driving force for the anterograde transport of RanGTP, we first examined the localization of RanGTP and actin waves in fixed neurons.…”

Section: Actin Waves Transport Gtp-bound Ran Towards the Neurite Tipmentioning

confidence: 99%

Ran GTPase regulates non-centrosomal microtubule nucleation and is transported by actin waves towards the neurite tip

Huang

Hsu

Chiu

et al. 2019

Preprint

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Microtubule (MT) is the most abundant cytoskeleton in neurons and controls multiple facets of their development. While the organizing center of MTs in mitotic cells is typically located at the centrosome, MT nucleation in post-mitotic neurons switches to non-centrosomal sites. A handful of proteins and organelle have been shown to promote non-centrosomal MT formation in neurons, yet the regulation mechanism remains unknown. Here we demonstrate that the small GTPase Ran is a key regulator of non-centrosomal MT nucleation in neurons. The GTP-bound Ran (RanGTP) localizes to the neurite tips and around the soma. Using the RanGTPand RanGDP-mimic mutants, we show that RanGTP promotes MT nucleation at the tip of the neurite. To demonstrate that RanGTP can promote MT nucleation in regions other than the neurite tip, an optogenetic tool called RanTRAP was constructed to enable light-induced local production of RanGTP in the neuronal cytoplasm. An increase of non-centrosomal MT nucleation can be observed by elevating the RanGTP level along the neurite using RanTRAP, establishing a new role for Ran in regulating neuronal MTs. Additionally, the mechanism of RanGTP enrichment at the neurite tip was examined. We discovered that actin waves drive the anterograde transport of RanGTP towards the neurite tip. Pharmacological disruption of actin waves abolishes the enrichment of RanGTP and reduces the non-centrosomal MT nucleation at the neurite tip. These observations provide a novel regulation mechanism of MTs and an indirect connection between the actin and MT cytoskeletons in neurons.

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Advanced Materials in Wireless, Implantable Electrical Stimulators that Offer Rapid Rates of Bioresorption for Peripheral Axon Regeneration

Guo

D’Andrea

Zhao

et al. 2021

Adv Funct Materials

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Injured peripheral nerves typically exhibit unsatisfactory and incomplete functional outcomes, and there are no clinically approved therapies for improving regeneration. Post-operative electrical stimulation (ES) increases axon regrowth, but practical challenges, from the cost of extended operating room time to the risks and pitfalls associated with transcutaneous wire placement, have prevented broad clinical adoption. This study presents a possible solution in the form of advanced bioresorbable materials for a type of thin, flexible, wireless implant that provides precisely controlled ES of the injured nerve for a brief time in the immediate post-operative period. Afterward, rapid, complete, and safe modes of bioresorption naturally and quickly eliminate all of the constituent materials in their entirety, without the need for surgical extraction. The unusually high rate of bioresorption follows from the use of a unique, bilayer enclosure that combines two distinct formulations of a biocompatible form of polyanhydride as an encapsulating structure, to accelerate the resorption of active components and confine fragments until complete resorption. Results from mouse models of tibial nerve transection with re-anastomosis indicate that this system offers levels of performance and efficacy that match those of conventional wired stimulators, but without the need to extend the operative period or to extract the device hardware.

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Actin Waves: Origin of Cell Polarization and Migration?

Cited by 127 publications

References 76 publications

Cell protrusion and retraction driven by fluctuations in actin polymerization: A two‐dimensional model

Cell protrusion and retraction driven by fluctuations in actin polymerization: A two‐dimensional model

Ran GTPase regulates non-centrosomal microtubule nucleation and is transported by actin waves towards the neurite tip

Advanced Materials in Wireless, Implantable Electrical Stimulators that Offer Rapid Rates of Bioresorption for Peripheral Axon Regeneration

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