Gradients of PI(4,5)P(2) and PI(3,5)P(2) Jointly Participate in Shaping the Back State of Dictyostelium Cells.

Gradients of PI(4,5)P(2) and PI(3,5)P(2) Jointly Participate in Shaping the Back State of Dictyostelium Cells.
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PI(4,5)P2和PI(3,5)P2的梯度共同参与盘基网柄菌细胞背面状态的塑造

DOI:
10.3389/fcell.2022.835185
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发表时间:
2022
影响因子:
5.5
通讯作者:
Cai H
Cai H
中科院分区:
生物学2区
文献类型:
--
作者:
Li D;Sun F;Yang Y;Tu H;Cai H

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极性是指细胞中分子或结构的不对称性,对不同的细胞功能至关重要。网骨藻已被证明是一个有价值的系统解剖细胞极性的分子机制。先前在网骨藻中的研究已经揭示了一系列信号和细胞骨架蛋白,其在前沿发挥作用以促进伪足延伸和迁移。相比之下,蛋白质是如何定位到后缘的还没有很好的理解。通过筛选不对称定位的蛋白质,我们确定了一个新的后缘蛋白,我们命名为Teep1。我们表明,由两个普列克底物蛋白同源(PH)结构域在Teep1形成的带电表面是必要的和足够的靶向它的后方的细胞。结合生物化学和成像分析,我们表明,Teep1在体外优先与PI(4,5)P2和PI(3,5)P2相互作用,同时消除细胞中的这些脂质物质阻断了Teep1的膜结合。此外,前缘局部肌管蛋白磷酸酶可能介导从前部去除PI(3,5)P2,以及形成PI(3,5)P2的从后到前梯度。总之,我们的数据表明,PI(4,5)P2和PI(3,5)P2的质膜共同参与塑造的后状态的网骨细胞。
Polarity, which refers to the molecular or structural asymmetry in cells, is essential for diverse cellular functions. Dictyostelium has proven to be a valuable system for dissecting the molecular mechanisms of cell polarity. Previous studies in Dictyostelium have revealed a range of signaling and cytoskeletal proteins that function at the leading edge to promote pseudopod extension and migration. In contrast, how proteins are localized to the trailing edge is not well understood. By screening for asymmetrically localized proteins, we identified a novel trailing-edge protein we named Teep1. We show that a charged surface formed by two pleckstrin homology (PH) domains in Teep1 is necessary and sufficient for targeting it to the rear of cells. Combining biochemical and imaging analyses, we demonstrate that Teep1 interacts preferentially with PI(4,5)P2 and PI(3,5)P2 in vitro and simultaneous elimination of these lipid species in cells blocks the membrane association of Teep1. Furthermore, a leading-edge localized myotubularin phosphatase likely mediates the removal of PI(3,5)P2 from the front, as well as the formation of a back-to-front gradient of PI(3,5)P2. Together our data indicate that PI(4,5)P2 and PI(3,5)P2 on the plasma membrane jointly participate in shaping the back state of Dictyostelium cells.
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