Calcium Bursts Allow Rapid Reorganization of EFhD2/Swip-1 Cross-linked Actin Networks in Epithelial Wound Closure

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 6

PMID 35524157

Authors

Franziska Lehne

Thomas Pokrant

Sabnam Parbin

Gabriela Salinas

Jorg Grosshans

Katja Rust

Jan Faix

Sven Bogdan

Affiliations

Soon will be listed here.

Abstract

Changes in cell morphology require the dynamic remodeling of the actin cytoskeleton. Calcium fluxes have been suggested as an important signal to rapidly relay information to the actin cytoskeleton, but the underlying mechanisms remain poorly understood. Here, we identify the EF-hand domain containing protein EFhD2/Swip-1 as a conserved lamellipodial protein strongly upregulated in Drosophila macrophages at the onset of metamorphosis when macrophage behavior shifts from quiescent to migratory state. Loss- and gain-of-function analysis confirm a critical function of EFhD2/Swip-1 in lamellipodial cell migration in fly and mouse melanoma cells. Contrary to previous assumptions, TIRF-analyses unambiguously demonstrate that EFhD2/Swip-1 proteins efficiently cross-link actin filaments in a calcium-dependent manner. Using a single-cell wounding model, we show that EFhD2/Swip-1 promotes wound closure in a calcium-dependent manner. Mechanistically, our data suggest that transient calcium bursts reduce EFhD2/Swip-1 cross-linking activity and thereby promote rapid reorganization of existing actin networks to drive epithelial wound closure.

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References

Huh Y, Oh S, Yeo Y, Chae I, Kim S, Lee J . Swiprosin-1 stimulates cancer invasion and metastasis by increasing the Rho family of GTPase signaling. Oncotarget. 2015; 6(15):13060-71. PMC: 4536999. DOI: 10.18632/oncotarget.3637. View

Jansen S, Collins A, Yang C, Rebowski G, Svitkina T, Dominguez R . Mechanism of actin filament bundling by fascin. J Biol Chem. 2011; 286(34):30087-96. PMC: 3191048. DOI: 10.1074/jbc.M111.251439. View

Thylur R, Gowda R, Mishra S, Jun C . Swiprosin-1: Its Expression and Diverse Biological Functions. J Cell Biochem. 2017; 119(1):150-156. DOI: 10.1002/jcb.26199. View

Pollard T . Actin and Actin-Binding Proteins. Cold Spring Harb Perspect Biol. 2016; 8(8). PMC: 4968159. DOI: 10.1101/cshperspect.a018226. View

Papalazarou V, Machesky L . The cell pushes back: The Arp2/3 complex is a key orchestrator of cellular responses to environmental forces. Curr Opin Cell Biol. 2020; 68:37-44. PMC: 7938217. DOI: 10.1016/j.ceb.2020.08.012. View

Wood W, Jacinto A, Grose R, Woolner S, Gale J, Wilson C . Wound healing recapitulates morphogenesis in Drosophila embryos. Nat Cell Biol. 2002; 4(11):907-12. DOI: 10.1038/ncb875. View

Spudich J, Watt S . The regulation of rabbit skeletal muscle contraction. I. Biochemical studies of the interaction of the tropomyosin-troponin complex with actin and the proteolytic fragments of myosin. J Biol Chem. 1971; 246(15):4866-71. View

Soliman A, Umstead A, Grabinski T, Kanaan N, Lee A, Ryan J . EFhd2 brain interactome reveals its association with different cellular and molecular processes. J Neurochem. 2021; 159(6):992-1007. PMC: 9552186. DOI: 10.1111/jnc.15517. View

Mun S, Park J, Park K, Lee Y, Kang J, Park T . Structural and Biochemical Characterization of EFhd1/Swiprosin-2, an Actin-Binding Protein in Mitochondria. Front Cell Dev Biol. 2021; 8:628222. PMC: 7848108. DOI: 10.3389/fcell.2020.628222. View

10.

Brinkman E, Chen T, Amendola M, van Steensel B . Easy quantitative assessment of genome editing by sequence trace decomposition. Nucleic Acids Res. 2014; 42(22):e168. PMC: 4267669. DOI: 10.1093/nar/gku936. View

11.

Abreu-Blanco M, Verboon J, Parkhurst S . Cell wound repair in Drosophila occurs through three distinct phases of membrane and cytoskeletal remodeling. J Cell Biol. 2011; 193(3):455-64. PMC: 3087011. DOI: 10.1083/jcb.201011018. View

12.

Moreira C, Jacinto A, Prag S . Drosophila integrin adhesion complexes are essential for hemocyte migration in vivo. Biol Open. 2013; 2(8):795-801. PMC: 3744071. DOI: 10.1242/bio.20134564. View

13.

Pinotsis N, Zielinska K, Babuta M, Arolas J, Kostan J, Khan M . Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. Proc Natl Acad Sci U S A. 2020; 117(36):22101-22112. PMC: 7486759. DOI: 10.1073/pnas.1917269117. View

14.

Stephan R, Gohl C, Fleige A, Klambt C, Bogdan S . Membrane-targeted WAVE mediates photoreceptor axon targeting in the absence of the WAVE complex in Drosophila. Mol Biol Cell. 2011; 22(21):4079-92. PMC: 3204070. DOI: 10.1091/mbc.E11-02-0121. View

15.

Moreno-Layseca P, Jantti N, Godbole R, Sommer C, Jacquemet G, Al-Akhrass H . Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis. Nat Cell Biol. 2021; 23(10):1073-1084. PMC: 7617174. DOI: 10.1038/s41556-021-00767-x. View

16.

Vuadens F, Rufer N, Kress A, Corthesy P, Schneider P, Tissot J . Identification of swiprosin 1 in human lymphocytes. Proteomics. 2004; 4(8):2216-20. DOI: 10.1002/pmic.200300779. View

17.

Yang C, Svitkina T . Visualizing branched actin filaments in lamellipodia by electron tomography. Nat Cell Biol. 2011; 13(9):1012-3. PMC: 3407679. DOI: 10.1038/ncb2321. View

18.

Kage F, Winterhoff M, Dimchev V, Mueller J, Thalheim T, Freise A . FMNL formins boost lamellipodial force generation. Nat Commun. 2017; 8:14832. PMC: 5364437. DOI: 10.1038/ncomms14832. View

19.

Giganti A, Plastino J, Janji B, Van Troys M, Lentz D, Ampe C . Actin-filament cross-linking protein T-plastin increases Arp2/3-mediated actin-based movement. J Cell Sci. 2005; 118(Pt 6):1255-65. DOI: 10.1242/jcs.01698. View

20.

Laevsky G, Knecht D . Cross-linking of actin filaments by myosin II is a major contributor to cortical integrity and cell motility in restrictive environments. J Cell Sci. 2003; 116(Pt 18):3761-70. DOI: 10.1242/jcs.00684. View