Chemotaxis in the absence of PIP3 gradients
Chemotaxis in the absence of PIP3 gradients
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DOI：
10.1016/j.cub.2007.04.004
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发表时间：
2007-05-01
期刊：
影响因子：
9.2
通讯作者：
Kay, Robert R.
中科院分区：
文献类型：
--
作者：
Hoeller, Oliver;Kay, Robert R.
趋化性中性粒细胞和变形网骨藻在其质膜中以梯度产生信号脂质PI（3，4，5）P3（PIP 3）[1-3]，其与外部趋化性梯度一起定向，并且已被提出充当内部指南针，引导细胞的运动[4，5]。支持和反对这一观点的证据都存在，但在所有情况下，这取决于抑制剂或基因敲除的使用，这可能只是不完全消除PIP 3梯度。我们已经创建了一个多基因敲除菌株中的Dictyosteoblasts缺乏所有五个1型磷酸肌醇3-激酶编码的基因组和PTEN磷酸酶，从而消除了所有已知的方式为化学引诱物产生PIP 3梯度质膜。由此产生的六倍体突变体能够以接近野生型的效率对环状AMP进行化学调节，并在没有明显缺陷的情况下触发肌动蛋白聚合。然而，在趋化性中，特别是在随机运动中，运动速度存在一致的缺陷。这项工作表明，膜PIP 3的极化对于精确的趋化性不是必需的，但它可以影响细胞速度。必须存在能够独立于极化的PIP 3和1型磷酸肌醇3-激酶引导细胞的从受体到细胞骨架的信号传导途径。
Chemotaxing neutrophils and Dictyostelium amoebae produce in their plasma membranes the signaling lipid PI(3,4,5)P3 (PIP3) in gradients [1-3], which are orientated with the external chemotactic gradient and have been proposed to act as an internal compass, guiding movement of the cell [4, 5]. Evidence for and against this idea exists, but in all cases it depends on the use of inhibitors or gene knockouts, which may only incompletely abolish the PIP3 gradient. We have created a multiple gene-knockout strain in Dictyostelium lacking all five type-1 phosphoinositide 3-kinases encoded in the genome and the PTEN phosphatase and have thus removed all known ways for chemoattractant to produce PIP3 gradients in the plasma membrane. The resulting sextuple mutant is able to chemotax to cyclic-AMP with near wild-type efficiency and to trigger actin polymerization without apparent defect. There is, however, a consistent defect in movement speed in chemotaxis and especially in random movement. This work shows that polarization of membrane PIP3 is not necessary for accurate chemotaxis, but it can affect cell speed. A signaling pathway from receptor to cytoskeleton able to guide cells independently of polarized PIP3 and type-1 phosphoinositide 3-kinases must exist.