SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells
SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells
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DOI：
10.1242/jcs.179663
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发表时间：
2016-03-15
影响因子：
4
通讯作者：
Erneux, Christophe
中科院分区：
文献类型：
--
作者：
Edimo, William's Elong;Ghosh, Somadri;Erneux, Christophe
磷酸肌醇，特别是磷脂酰肌醇（3，4，5）三磷酸[PI（3，4，5）P3]和磷脂酰肌醇4，5二磷酸[PI（4，5）P2]，由SHIP 2（也称为INPPL 1）识别，SHIP 2是肌醇多磷酸5-磷酸酶家族的成员。SHIP 2使PI（3，4，5）P3去磷酸化以形成PI（3，4）P2;后者与特异性靶蛋白（例如，板脂蛋白）相互作用。尽管优选的SHIP 2底物是PI（3，4，5）P3，但PI（4，5）P2也可以被该酶脱磷酸化为磷脂酰肌醇4-磷酸（PI 4P）。通过耗尽胶质母细胞瘤细胞系1321 N1中的SHIP 2，我们表明SHIP 2抑制细胞迁移。在不同的胶质母细胞瘤细胞系和原代培养物中，SHIP 2在质膜上的染色与PI（4，5）P2免疫反应性部分重叠。PI（4，5）P2在SHIP 2缺陷的N1细胞中与对照细胞相比上调;相反，PI 4P在SHIP 2缺陷的细胞中非常低。因此，SHIP 2控制完整细胞中的PI（3，4，5）P3和PI（4，5）P2水平。在1321 N1细胞中，PI（4，5）P2结合蛋白myosin-1c被鉴定为SHIP 2的新相互作用物。SHIP 2对PI（4，5）P2和PI 4 P含量的调节通过组织局灶性粘连来控制1321 N1细胞迁移。因此，我们的研究结果揭示了SHIP 2在PTEN缺陷型胶质母细胞瘤1321 N1细胞中控制PI（4，5）P2、PI 4P和细胞迁移中的新作用。
Phosphoinositides, particularly phosphatidylinositol (3,4,5)trisphosphate [PI(3,4,5)P3] and phosphatidylinositol 4,5bisphosphate [PI(4,5)P2], are recognized by SHIP2 (also known as INPPL1) a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the latter interacts with specific target proteins (e.g. lamellipodin). Although the preferred SHIP2 substrate is PI(3,4,5)P3, PI(4,5)P2 can also be dephosphorylated by this enzyme to phosphatidylinositol 4-phosphate (PI4P). Through depletion of SHIP2 in the glioblastoma cell line 1321 N1, we show that SHIP2 inhibits cell migration. In different glioblastoma cell lines and primary cultures, SHIP2 staining at the plasma membrane partly overlaps with PI(4,5)P2 immunoreactivity. PI(4,5)P2 was upregulated in SHIP2-deficient N1 cells as compared to control cells; in contrast, PI4P was very much decreased in SHIP2-deficient cells. Therefore, SHIP2 controls both PI(3,4,5)P3 and PI(4,5)P2 levels in intact cells. In 1321 N1 cells, the PI(4,5)P2-binding protein myosin-1c was identified as a new interactor of SHIP2. Regulation of PI(4,5)P2 and PI4P content by SHIP2 controls 1321 N1 cell migration through the organization of focal adhesions. Thus, our results reveal a new role of SHIP2 in the control of PI(4,5)P2, PI4P and cell migration in PTEN-deficient glioblastoma 1321 N1 cells.