Activation of cytosolic Slingshot-1 phosphatase by gelsolin-generated soluble actin filaments
Activation of cytosolic Slingshot-1 phosphatase by gelsolin-generated soluble actin filaments
复制标题
凝溶胶蛋白生成的可溶性肌动蛋白丝激活胞质 Slingshot-1 磷酸酶
DOI：
10.1016/j.bbrc.2014.10.108
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kensaku Mizuno
中科院分区：
文献类型：
--
作者：
Katsunori Takahashi;Shin-ichiro Kannno;Kensaku Mizuno
Slingshot-1（SSH 1）是一种蛋白磷酸酶，其去磷酸化并激活肌动蛋白切割和分解蛋白cofilin。SSH 1与F-肌动蛋白结合并被其激活，而不是G-肌动蛋白。SSH 1在富含F-肌动蛋白的板状伪足中积累，但也弥散分布在细胞质中。目前尚不清楚SSH 1是否被细胞质中的可溶性（低水平聚合）肌动蛋白丝激活。在这项研究中，我们表明，SSH 1结合凝溶胶蛋白通过肌动蛋白丝的胞质组分。凝溶胶蛋白促进溶解的肌动蛋白丝和SSH 1在无细胞测定和培养的细胞。SSH 1被凝溶胶蛋白产生的可溶性肌动蛋白丝激活。此外，凝溶胶蛋白增强cofilin去磷酸化神经调节蛋白刺激的细胞。我们的研究结果表明，胞质SSH 1形成一个复杂的凝溶胶蛋白通过可溶性肌动蛋白丝和激活凝溶胶蛋白产生的可溶性肌动蛋白丝和凝溶胶蛋白促进刺激诱导的cofilin去磷酸化，通过增加可溶性肌动蛋白丝，支持SSH 1在细胞质中的激活。
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.