tsunami, the Dictyostelium homolog of the Fused kinase, is required for polarization and chemotaxis
tsunami, the Dictyostelium homolog of the Fused kinase, is required for polarization and chemotaxis
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DOI：
10.1101/gad.1694508
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发表时间：
2008-08-15
影响因子：
10.5
通讯作者：
Devreotes, Peter N.
中科院分区：
文献类型：
--
作者：
Tang, Linnan;Franca-Koh, Jonathan;Devreotes, Peter N.
在对盘状盘齿龙趋化突变的正向遗传筛选中，我们发现了一个功能丧失突变，命名为海啸，编码融合激酶的同源物。缺乏tsuA功能的细胞不能有效地发挥趋化作用，不能在趋化梯度中形成极化或正确定向的伪足。虽然tsuA（-）细胞能够将受体占用与磷脂酰肌醇（3,4,5）三磷酸（PIP3）的产生和肌动蛋白聚合偶联，但PIP3反应延长，基础f -肌动蛋白水平升高。有趣的是，twa定位于微管网络和主要在细胞周围发现的点。对该基因的分析发现了一个新的c端结构域，我们将其命名为海啸同源（TH）结构域。激酶结构域和TH结构域都是拯救tsuA（-）细胞表型缺陷所必需的。虽然激酶活性不是微管定位所必需的，但TH结构域是必不可少的。因此，激酶活性定位于微管对TsuA功能至关重要。我们提出，与微管网络相关的功能可能是融合激酶蛋白在不同生物体中不同作用的基础。
In a forward genetic screen for chemotaxis mutants in Dictyostelium discoideum, we identified a loss-of-function mutation, designated tsunami, encoding a homolog of the Fused kinase. Cells lacking tsuA function could not effectively perform chemotaxis and were unable to become polarized or correctly orient pseudopods in chemotactic gradients. While tsuA(-) cells were able to couple receptor occupancy to phosphatidylinositol (3,4,5) trisphosphate (PIP3) production and actin polymerization, the PIP3 response was prolonged and basal F-actin levels were increased. Interestingly, TsuA localizes to the microtubule network and puncta mainly found at the cell periphery. Analysis of the gene uncovered a novel C-terminal domain that we designated the Tsunami Homology (TH) domain. Both the kinase domain and the TH domain are required to rescue the phenotypic defects of tsuA(-) cells. While kinase activity is not required for localization to microtubules, the TH domain is essential. Thus, localization of kinase activity to microtubules is critical for TsuA function. We propose that functions in association with the microtubule network may underlie the divergent roles of Fused kinase proteins in different organisms.