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 coffin 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. (C) 2014 Elsevier Inc. All rights reserved.
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Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USANorthwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
Liu, Shu Q.
Tefft, Brandon J.
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Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USANorthwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
Tefft, Brandon J.
Zhang, Andy
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Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USANorthwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
Zhang, Andy
Zhang, Li-qun
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Northwestern Univ, Sensory Motor Performance Program, Dept Phys Med & Rehabil, Chicago, IL 60611 USANorthwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
Zhang, Li-qun
Wu, Yu H.
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Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USANorthwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA