Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to cofilin
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Cellular and Molecular Life Sciences
Research Article
Swiprosin‑1 modulates actin dynamics by regulating the F‑actin accessibility to cofilin Yun Hyun Huh · So Hee Kim · Kyoung‑Hwun Chung · Sena Oh · Min‑Sung Kwon · Hyun‑Woo Choi · Sangmyung Rhee · Je‑Hwang Ryu · Zee Yong Park · Chang‑Duk Jun · Woo Keun Song
Received: 12 March 2013 / Revised: 31 July 2013 / Accepted: 2 August 2013 / Published online: 21 August 2013 © The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract Membrane protrusions, like lamellipodia, and cell movement are dependent on actin dynamics, which are regulated by a variety of actin-binding proteins acting cooperatively to reorganize actin filaments. Here, we provide evidence that Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to a loss of actin stress fibers at the leading edges of cells but not in the cell cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered F-actin, which remodeled the structural organization of actin filaments making them inaccessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at Ser183, a phosphorylation site newly identified using mass spectrometry, effectively inhibited clustering of actin filaments and permitted cofilin access to Electronic supplementary material The online version of this article (doi:10.1007/s00018-013-1447-5) contains supplementary material, which is available to authorized users. Y. H. Huh · S. H. Kim · K.-H. Chung · S. Oh · M.-S. Kwon · H.-W. Choi · Z. Y. Park · C.-D. Jun · W. K. Song (*) Bio Imaging and Cell Dynamics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500712, Korea e-mail: [email protected] S. Rhee School of Biological Sciences, Joong Ang University, Seoul 156756, Korea J.-H. Ryu Research Center for Biomineralization Disorders and Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 500757, Korea
F-actin, resulting in actin depolymerization. Cells overexpressing a Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient mutant exhibited irregular membrane dynamics during the protrusion and retraction cycles of lamellipodia. Taken together, these findings suggest that dynamic exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel mechanism that regulates actin dynamics by modulating the pattern of cofilin activity at the leading edges of cells. Keywords Swiprosin-1 · Actin filament · Cofilin · Lamellipodia
Introduction The membrane protrusions and lamellipodia necessary for cell migration have a highly dynamic actin structure that is characterized by the rapid turnover of actin filaments. These actin dynamics are regulated by a variety of actin-binding proteins t
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