title: Activation of cytosolic Slingshot-1 phosphatase by gelsolin-generated soluble actin filaments.
abstract: Slingshot-1 (SSH1) is a protein phosphatase that dephosphorylates and activates cofilin, an actin-severing and -disassembling protein. SSH1 is bound to and activated by F-actin, but not G-actin. SSH1 is accumulated in the F-actin-rich lamellipodium but is also diffusely distributed in the cytoplasm. It remains unknown whether SSH1 is activated by soluble (low-level polymerized) actin filaments in the cytoplasm. In this study, we show that SSH1 binds to gelsolin via actin filaments in the cytosolic fraction. Gelsolin promoted solubilization of actin filaments and SSH1 in cell-free assays and in cultured cells. SSH1 was activated by gelsolin-generated soluble actin filaments. Furthermore, gelsolin enhanced cofilin dephosphorylation in neuregulin-stimulated cells. Our results suggest that cytosolic SSH1 forms a complex with gelsolin via soluble actin filaments and is activated by gelsolin-generated soluble actin filaments and that gelsolin promotes stimulus-induced cofilin dephosphorylation through increasing soluble actin filaments, which support SSH1 activation in the cytoplasm.
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kanno
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan. Electronic address: kmizuno@biology.tohoku.ac.jp.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Mizuno
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D004789:Enzyme Activation; D018260:Gelsolin / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D060066:Protein Interaction Maps; D012995:Solubility
chemical_list: D051339:Actin Depolymerizing Factors; D018260:Gelsolin; D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human
keywords: Actin oligomers; Cofilin; Gelsolin; Phosphatase; Scinderin; Slingshot