title: Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to cofilin.
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 in accessible 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 over expressing 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.
authors: Yun Hyun
authors: YH
authors: Huh
authors: So Hee
authors: SH
authors: Kim
authors: Kyoung-Hwun
authors: KH
authors: Chung
authors: Sena
authors: S
authors: Oh
authors: Min-Sung
authors: MS
authors: Kwon
authors: Hyun-Woo
authors: HW
authors: Choi
authors: Sangmyung
authors: S
authors: Rhee
authors: Je-Hwang
authors: JH
authors: Ryu
authors: Zee Yong
authors: ZY
authors: Park
authors: Chang-Duk
authors: CD
authors: Jun
authors: Woo Keun
authors: WK
authors: Song
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C502299:EFHD2 protein, human; C530752:EFHD2 protein, mouse; D008840:Microfilament Proteins; D012694:Serine; D004815:Epidermal Growth Factor
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