A Dictyostelium homologue of WASP is required for polarized F-actin assembly during chemotaxis
A Dictyostelium homologue of WASP is required for polarized F-actin assembly during chemotaxis
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DOI：
10.1091/mbc.e04-09-0844
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发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Chung, CY
中科院分区：
文献类型：
--
作者：
Myers, SA;Han, JW;Chung, CY
肌动蛋白细胞骨架控制细胞的整体结构，并且在趋化细胞中高度极化，其中F-肌动蛋白主要组装在前前缘，并且在较小程度上组装在细胞的后部。Wiskott-Aldrich综合征蛋白（WASP）已成为控制肌动蛋白聚合的核心参与者。我们研究了WASP的功能及其在趋化性Dictyosteoblasts细胞中的调节，并证明了WASP在组织趋化性细胞中极化F-肌动蛋白组装中的特定和重要作用。表达极低水平WASP的细胞显示出降低的F-肌动蛋白水平和极化F-肌动蛋白组装的显著缺陷，导致在趋化过程中无法建立轴向极性。GFP-WASP优先定位于趋化细胞的前缘和尾足，并且WASP的B结构域是WASP定位所必需的。我们证明了B结构域以相似的亲和力与PI（4，5）P-2和PI（3，4，5）P-3结合。B结构域与PI（3，4，5）P-3之间的相互作用对WASP在趋化细胞前缘的定位起重要作用。我们的研究结果表明，WASP的定位和激活的空间和时间控制是必不可少的定向运动的调节。
The actin cytoskeleton controls the overall structure of cells and is highly polarized in chemotaxing cells, with F-actin assembled predominantly in the anterior leading edge and to a lesser degree in the cell's posterior. Wiskott-Aldrich syndrome protein (WASP) has emerged as a central player in controlling actin polymerization. We have investigated WASP function and its regulation in chemotaxing Dictyostelium cells and demonstrated the specific and essential role of WASP in organizing polarized F-actin assembly in chemotaxing cells. Cells expressing very low levels of WASP show reduced F-actin levels and significant defects in polarized F-actin assembly, resulting in an inability to establish axial polarity during chemotaxis. GFP-WASP preferentially localizes at the leading edge and uropod of chernotaxing cells and the B domain of WASP is required for the localization of WASP. We demonstrated that the B domain binds to PI(4,5)P-2 and PI(3,4,5)P-3 with similar affinities. The interaction between the B domain and PI(3,4,5)P-3 plays an important role for the localization of WASP to the leading edge in chernotaxing cells. Our results suggest that the spatial and temporal control of WASP localization and activation is essential for the regulation of directional motility.