PTEN regulates motility but not directionality during leukocyte chemotaxis
PTEN regulates motility but not directionality during leukocyte chemotaxis
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DOI：
10.1242/jcs.01545
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发表时间：
2004-12-01
影响因子：
4
通讯作者：
Mañes, S
中科院分区：
文献类型：
--
作者：
Lacalle, RA;Gómez-Moutón, C;Mañes, S
磷脂酰肌醇-3激酶和PTEN(第10号染色体上的磷酸酶和张力蛋白同源物)在相对的细胞极的定位控制着网柄苔藓的趋化性。为了在哺乳动物细胞中研究这一模型，我们分析了绿色荧光蛋白(GFP)标记的PTEN嵌合体在趋化过程中的动态重新分布。在趋化PTEN阴性的Jurkat细胞和PTEN阳性的HL60细胞的胞浆中均可见GFP标记的PTEN的N或C末端分布。此外，我们没有检测到内源性PTEN在化学诱导剂刺激的HL60细胞中的尾足积聚。细胞分离表明，内源性和异位表达的PTEN主要局限于胞浆，而化学诱导剂刺激不改变这一位置。PTEN在Jurkat细胞中的重新表达或在HL60细胞中被特定的siRNA缺失并不影响细胞梯度感知，但PTEN调节了趋化物质诱导的肌动蛋白聚合和细胞移动的速度。结果提示，在哺乳动物细胞趋化过程中，PTEN在调节肌动蛋白聚合中起作用，但不具有方向性。
The localization at opposite Cell poles of phosphatidylinositol-3 kinases and PTEN (phosphatase and tensin homolog on chromosome 10) governs Dictyostelium chemotaxis. To study this model in mammalian cells, we analyzed the dynamic redistribution of green fluorescent protein (GFP)-tagged PTEN chimeras during chemotaxis. N- or C-terminus GFP-tagged PTEN was distributed homogenously in the cytoplasm of chemotaxing PTEN-negative Jurkat cells and PTEN-positive HL60 cells. Moreover, we did not detect uropod accumulation of endogenous PTEN in chemoattractant-stimulated HL60 cells. Cell fractionation indicated that both endogenous and ectopically expressed PTEN were confined largely to the cytosol, and that chemoattractant stimulation did not alter this location. PTEN re-expression in Jurkat cells or PTEN depletion by specific siRNA in HL60 cells did not affect cell gradient sensing; PTEN nonetheless modulated chemoattractant-induced actin polymerization and the speed of cell movement. The results suggest a role for PTEN in regulating actin polymerization, but not directionality during mammalian cell chemotaxis.