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| Open AccessPPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex
The WAVE regulatory complex activates Arp2/3 at the cell cortex and in membrane protrusions to generate persistent cell migration. Here authors show that PPP2R1A, a scaffold subunit of protein phosphatase 2, associates with an alternative form of the WAVE complex where WAVE, the subunit that activates Arp2/3, is replaced by NHSL1.
- Yanan Wang
- , Giovanni Chiappetta
- & Alexis M. Gautreau
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Article
| Open AccessCalcium bursts allow rapid reorganization of EFhD2/Swip-1 cross-linked actin networks in epithelial wound closure
Calcium serves as an important second messenger in signal transduction to the actin cytoskeleton. Here, we identify EFhD2/Swip-1 as a calcium-dependent actin cross-linker promoting rapid reorganization of actin networks in epithelial wound closure.
- Franziska Lehne
- , Thomas Pokrant
- & Sven Bogdan
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Article
| Open AccessMolecular mechanism of Arp2/3 complex inhibition by Arpin
The Arp2/3 complex inhibitor Arpin controls cell migration by interrupting a feedback loop involving Rac-WAVE-Arp2/3 complex Here, the authors use structural, biochemical, and cellular studies to reveal Arpin’s mechanism of inhibition.
- Fred E. Fregoso
- , Trevor van Eeuwen
- & Roberto Dominguez
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| Open AccessNance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration
Cell migration is essential for many physiological processes. Its deregulation causes cancer metastasis and it is not well understood how it is tightly controlled. We identify NHSL1 as a negative regulator of actin nucleating Scar/WAVE-Arp2/3 complexes, cell protrusion stability, and cell migration.
- Ah-Lai Law
- , Shamsinar Jalal
- & Matthias Krause
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Article
| Open AccessA barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks
The assembly of branched actin networks depends on the heterodimeric capping protein CP/CapZ. Combining cryoEM, in vitro reconstitution and cell biological assays, the authors show that CP not only prevents actin filament elongation but also selectively masks actin filament ends to promote nucleation.
- Johanna Funk
- , Felipe Merino
- & Peter Bieling
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Article
| Open AccessCell migration guided by long-lived spatial memory
Cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix; the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here authors show that motile cells leave long-lived physicochemical footprints along their way, which determine their future path.
- Joseph d’Alessandro
- , Alex Barbier--Chebbah
- & Benoît Ladoux
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Article
| Open AccessT-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration
In vivo, cells migrate across a diverse landscape of extracellular matrix containing gaps which present a challenge for cells to protrude across. Here, the authors show that T-Plastin strengthens protrusive actin networks to promote protrusion, extracellular matrix gap-bridging, and cell migration.
- Damien Garbett
- , Anjali Bisaria
- & Tobias Meyer
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| Open AccessDeconvolution of subcellular protrusion heterogeneity and the underlying actin regulator dynamics from live cell imaging
Cell protrusion dynamics are heterogeneous at the subcellular level, but current analyses operate at the cellular or ensemble level. Here the authors develop a computational framework to quantify subcellular protrusion phenotypes and reveal the underlying actin regulator dynamics at the leading edge.
- Chuangqi Wang
- , Hee June Choi
- & Kwonmoo Lee
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Article
| Open AccessGlycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus
Defects in neural crest development cause neurocristopathies and cancer, but what regulates this is unclear. Here, the authors show that glycogen synthase kinase 3 (GSK3) regulates migration of neural crest cells, as shown on genetic deletion of GSK3 in the mouse, and that this acts via anaplastic lymphoma kinase.
- Sandra G. Gonzalez Malagon
- , Anna M. Lopez Muñoz
- & Karen J. Liu
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Article
| Open AccessNetwork heterogeneity regulates steering in actin-based motility
Protrusive cellular structures contain a heterogeneous density of actin, but whether this influences motility is not known. Using an in vitro system and modelling, here the authors show that local actin monomer depletion and network architecture can tune the rate of network growth to impose steering during motility.
- Rajaa Boujemaa-Paterski
- , Cristian Suarez
- & Laurent Blanchoin
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Article
| Open AccessFMNL formins boost lamellipodial force generation
Actin polymerization in lamellipodia of cells is regulated by the Arp2/3 complex and FMNL family formins. Here the authors show that both FMNL2 and FMNL3 contribute to lamellipodium protrusion and structure, and abolishing FMNL2/3 reduces protrusion force generation and migration, without affecting Arp2/3 incorporation.
- Frieda Kage
- , Moritz Winterhoff
- & Klemens Rottner
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Article
| Open AccessThe structure of FMNL2–Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation
FMNL formins polymerize actin filaments to generate cellular protrusions such as lamellipodia and filopodia at the leading edge of a cell. Here the authors provide detailed mechanistic insights into the formation of actin-based protrusions through GTPase dependent activation and membrane localization of FMNL1 and FMNL2.
- Sonja Kühn
- , Constanze Erdmann
- & Matthias Geyer
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Article
| Open AccessAugmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5
Augmented AMP-activated protein kinase (AMPK) activity inhibits cell migration through an unknown mechanism. Here, Yan et al.show that AMPK phosphorylates the novel substrate PDZ and LIM domain 5 (Pdlim5), and that phosphomimetic Pdlim5 impairs cell migration by disrupting the Rac1-Arp2/3 signalling pathway.
- Yi Yan
- , Osamu Tsukamoto
- & Seiji Takashima
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Article |
Synthetic polyamines promote rapid lamellipodial growth by regulating actin dynamics
While small molecules that destabilize actin filaments are readily available, artificially stimulating actin polymerization in cells typically involves genetic manipulation. Here, the authors design cell-permeable branched polyamines that promote lamellipodium formation by stimulating actin polymerization.
- Iliana Nedeva
- , Girish Koripelly
- & Daniel Riveline