Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to cofilin
| Autor: | Woo Keun Song, Zee Yong Park, Sena Oh, Min‑Sung Kwon, Yun Hyun Huh, Je-Hwang Ryu, Kyoung‑Hwun Chung, Hyunwoo Choi, Chang-Duk Jun, So Hee Kim, Sangmyung Rhee |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Arp2/3 complex
macromolecular substances Cellular and Molecular Neuroscience Actin remodeling of neurons Mice Serine Tumor Cells Cultured Animals Humans Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing Pharmacology Swiprosin-1 biology Epidermal Growth Factor Calcium-Binding Proteins Cell Membrane Microfilament Proteins Actin remodeling Cell Biology Cofilin Lamellipodia Actins Cell biology Profilin Actin Depolymerizing Factors biology.protein Molecular Medicine MDia1 Actin filament Lamellipodium Filopodia Research Article Signal Transduction |
| Zdroj: | Cellular and Molecular Life Sciences |
| ISSN: | 1420-9071 1420-682X |
| Popis: | 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 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. 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. |
| Databáze: | OpenAIRE |
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