Spatiotemporal dynamics of traction forces show three contraction centers in migratory neurons

Jiang, Jian; Zhang, Zhenghong; Yuan, Xiao-bing; Poo, Mu‐ming

doi:10.1084/jem.2127oia54

Cited by 6 publications

(8 citation statements)

References 28 publications

(32 reference statements)

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“…Figure 5B and Video S4 show representative force mapping under a migrating WT neuroblast. Notably, prominent traction forces were observed under the growth cone of the leading processes (arrows 1, bead 5, Figure 5B), as reported in cerebellar granule cells (Jiang et al, 2015). The shaft of the leading processes did not produce remarkable forces.…”

Section: Shootin1b Is Involved In the Generation Of Traction Force At The Leading Process Growth Conesupporting

confidence: 68%

“…Our force-mapping analyses revealed prominent traction forces under the leading process growth cone of migrating olfactory interneurons (Figure 5B). Traction forces under the leading process growth cone have also been reported in cerebellar granular cells (Jiang et al, 2015). The direction of the forces was oriented toward the rear of the cells (Figure 5D), and their magnitude showed a positive correlation with growth cone advance (Figure 5E), suggesting that driving force for the growth cone advance (rightmost black arrow, Figure 7H) is produced as a counterforce to the traction forces exerted on the substrate (yellow arrows).…”

Section: Molecular Mechanics Of Shootin1b-mediated Neuronal Migrationsupporting

confidence: 57%

“…Mechanical coupling between the F-actin retrograde flow and cell-adhesion molecules by clutch molecules transmits the force of F-actin flow to the adhesive substrate, thereby generating the traction force to propel axonal growth cone migration (Mitchison and Kirschner, 1988;Suter and Forscher, 2000;Bard et al, 2008;Chan and Odde, 2008;Shimada et al, 2008;Lowery and Van Vactor, 2009;Garcia et al, 2015;Baba et al, 2018). Previous studies with migratory cerebellar granule cells reported F-actin retrograde flow (He et al, 2010) and traction force (Jiang et al, 2015) at the leading process growth cone. However, whether clutch molecules are utilized in neuronal cell migration remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration

et al. 2018

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As an essential step for brain morphogenesis, neurons migrate via mechanical interactions with components of their environment such as neighboring cells and the extracellular matrix. However, the molecular mechanism by which neurons exert forces on their environment during migration remains poorly understood. Here, we show that shootin1b is expressed in migrating mouse olfactory interneurons and accumulates at their leading process growth cone. We demonstrate that shootin1b, by binding to cortactin and L1-CAM, couples F-actin retrograde flow and the adhesive substrate as a clutch molecule. Shoo-tin1b-mediated clutch coupling at the growth cone generates traction force on the substrate, thereby promoting leading process extension and subsequent somal translocation of olfactory interneurons. Furthermore, loss of shootin1 causes abnormal positioning of the interneurons and dysgenesis of the olfactory bulb. Our findings indicate that shootin1b plays a key role in force-driven leading process extension, which propels the migration of olfactory interneurons during olfactory bulb formation.

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Section: Shootin1b Is Involved In the Generation Of Traction Force At The Leading Process Growth Conesupporting

confidence: 68%

Section: Molecular Mechanics Of Shootin1b-mediated Neuronal Migrationsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

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Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration

et al. 2018

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“…Previous work establishes that treatment of cells with Calyculin A, an inhibitor of myosin light chain phosphatase, increases myosin II-dependent force generation [58][59][60] . We found that Ca 2+ flickers in the same set of HFFs before and after treatment with 10 nM Calyculin A showed on average of 5-fold increase in Ca 2+ flickers within minutes (Fig.…”

Section: Force Generation By Mlck-mediated Myosin II Phosphorylation mentioning

confidence: 89%

Myosin-II mediated traction forces evoke localized Piezo1 Ca²⁺ flickers

Ellefsen

Chang

Nourse

et al. 2018

Preprint

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Piezo channels transduce mechanical stimuli into electrical and chemical signals, and in doing so, powerfully influence development, tissue homeostasis, and regeneration. While much is known about how Piezo1 responds to external forces, its response to internal, cell-generated forces remains poorly understood. Here, using measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that actomyosin-based cellular traction forces generate spatially-restricted Ca 2+ flickers in the absence of externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched in regions proximal to force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca 2+ flickers allow spatial segregation of mechanotransduction events, and that diffusion allows channel molecules to efficiently respond to transient, local mechanical stimuli. Movie M1. Piezo1 Ca 2+ flickers are reduced in Piezo1-knockout HFFs. The movie shows an F/F 0 ratio movie of Ca 2+ flickers from WT and Piezo1-KO HFFs. Movie M2. Piezo1 Ca 2+ flickers are reduced in Piezo1-knockout MEFs. The movie shows an F/F 0 ratio movie of Ca 2+ flickers from WT and Piezo1-KO MEFs. Movie M3. Piezo1 Ca 2+ flickers imaged from HFFs. The movie shows the F/F 0 ratio movie from WT HFFs that was used for localization of Piezo1 Ca 2+ flickers in Fig. S2. Movie M4. Mobility of Piezo1-tdTomato puncta in mNSPCs imaged using TIRFM. Puncta visible outside the yellow cell line are from neighboring cells.

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“…Actomyosin is found to accumulate in either the proximal leading process or rear of the cell soma depending on the cell type, and local inactivation by drug treatment or laser ablation has demonstrated that the contractile tension of actomyosin is converted to a pulling or pushing force to the nucleus. [4][5][6][7][8][9] Microtubules have been shown to emanate from the leading process, where the centrosome is typically positioned, with the plus ends toward the cell soma. These microtubules are thought to associate with the nucleus and work as rails on which the cytoplasmic dynein motor carries the nucleus into the leading process by its minus end-directed motor activity.…”

mentioning

confidence: 99%

Dynamic Interaction Between Microtubules and the Nucleus Regulates Nuclear Movement During Neuronal Migration

Kengaku

2018

J Exp Neurosci

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Fine structures of the mammalian brain are formed by neuronal migration during development. Newborn neurons migrate long distances from the germinal zone to individual sites of function by squeezing their largest cargo, the nucleus, through the crowded neural tissue. Nuclear translocation is thought to be orchestrated by microtubules, actin, and their associated motor proteins, dynein and myosin. However, where and how the cytoskeletal forces are converted to actual nuclear movement remains unclear. Using high-resolution confocal imaging of live migrating neurons, we demonstrated that microtubule-dependent forces are directly applied to the nucleus via the linker of nucleoskeleton and cytoskeleton complex, and that they induce dynamic nuclear movement, including translocation, rotation, and local peaking. Microtubules bind to small points on the nuclear envelope via the minus- and plus-oriented motor proteins, dynein and kinesin-1, and generate a point force independent of the actin-dependent force. Dynamic binding of microtubule motors might cause a continuously changing net force vector acting on the nucleus and results in a stochastic and inconsistent movement of the nucleus, which are seen in crowded neural tissues.

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Spatiotemporal dynamics of traction forces show three contraction centers in migratory neurons

Cited by 6 publications

References 28 publications

Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration

Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration

Myosin-II mediated traction forces evoke localized Piezo1 Ca²⁺ flickers

Dynamic Interaction Between Microtubules and the Nucleus Regulates Nuclear Movement During Neuronal Migration

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Spatiotemporal dynamics of traction forces show three contraction centers in migratory neurons

Cited by 6 publications

References 28 publications

Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration

Shootin1b Mediates a Mechanical Clutch to Produce Force for Neuronal Migration

Myosin-II mediated traction forces evoke localized Piezo1 Ca2+ flickers

Dynamic Interaction Between Microtubules and the Nucleus Regulates Nuclear Movement During Neuronal Migration

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Product

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Myosin-II mediated traction forces evoke localized Piezo1 Ca²⁺ flickers