Role of Phosphatidylinositol 3-Kinases in Chemotaxis in Dictyostelium*
Role of Phosphatidylinositol 3-Kinases in Chemotaxis in Dictyostelium*
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磷脂酰肌醇 3-激酶在盘基网柄菌趋化作用中的作用*
DOI：
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发表时间：
2007
影响因子：
4.8
通讯作者：
R. Firtel
中科院分区：
文献类型：
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作者：
K. Takeda;A. Sasaki;H. Ha;Hyun;R. Firtel
在几种细胞类型中的实验表明，磷脂酰肌醇3，4，5-三磷酸的局部积累介导细胞在梯度传感期间迁移的能力。我们采取了一个系统的方法来表征的功能，6个推定的I类磷脂酰肌醇3-激酶（PI 3 K1 -6）在网骨藻创建一系列的基因敲除。这些研究表明，PI 3 K1-PI 3 K3是化学引诱剂介导的磷脂酰肌醇3，4，5-三磷酸产生的主要PI 3 K。我们研究了趋化性的pi 3 k1/2/3三重敲除菌株（pi 3 k1/2/3空细胞）cAMP在两个不同的实验条件下，从微量移液管和浅，线性梯度在Dunn室发射的指数梯度，使用四个cAMP浓度范围超过10000倍。在所有测试条件下，p13 k1/2/3无效细胞移动较慢，极性低于野生型细胞。PI 3 K1/2/3无效细胞向微量吸管发出的化学引诱物移动，尽管持续性低于野生型或PI 3 K1/2无效细胞。在浅的线性梯度，pi 3 k1/2空细胞有更大的方向性缺陷，特别是在较低的化学引诱剂浓度。我们的研究表明，虽然PI 3 K在某些化学引诱物条件下对定向运动不是必不可少的，但它是定向传感途径的关键组成部分，在线性化学引诱物梯度中起着关键作用，特别是在低化学引诱物浓度下。PI 3 K在趋化性中的相对重要性也取决于细胞的发育阶段。我们的数据表明，当细胞感知到强信号时，其他信号通路的输出足以介导方向感测，但PI 3 K信号对于检测较弱的信号至关重要。
Experiments in several cell types revealed that local accumulation of phosphatidylinositol 3,4,5-triphosphate mediates the ability of cells to migrate during gradient sensing. We took a systematic approach to characterize the functions of the six putative Class I phosphatidylinositol 3-kinases (PI3K1–6) in Dictyostelium by creating a series of gene knockouts. These studies revealed that PI3K1–PI3K3 are the major PI3Ks for chemoattractant-mediated phosphatidylinositol 3,4,5-triphosphate production. We studied chemotaxis of the pi3k1/2/3 triple knock-out strain (pi3k1/2/3 null cells) to cAMP under two distinct experimental conditions, an exponential gradient emitted from a micropipette and a shallow, linear gradient in a Dunn chamber, using four cAMP concentrations ranging over a factor of 10,000. Under all conditions tested pi3k1/2/3 null cells moved slower and had less polarity than wild-type cells. pi3k1/2/3 null cells moved toward a chemoattractant emitted by a micropipette, although persistence was lower than that of wild-type or pi3k1/2 null cells. In shallow linear gradients, pi3k1/2 null cells had greater directionality defects, especially at lower chemoattractant concentrations. Our studies suggest that although PI3K is not essential for directional movement under some chemoattractant conditions, it is a key component of the directional sensing pathway and plays a critical role in linear chemoattractant gradients, especially at low chemoattractant concentrations. The relative importance of PI3K in chemotaxis is also dependent on the developmental stage of the cells. Our data suggest that the output of other signaling pathways suffices to mediate directional sensing when cells perceive a strong signal, but PI3K signaling is crucial for detecting weaker signals.
影响因子：
3.3
作者：
Lee, S;Comer, FI;Firtel, RA
通讯作者：
Firtel, RA
影响因子：
11.8
作者：
Janetopoulos, C;Borleis, J;Devreotes, P
通讯作者：
Devreotes, P
影响因子：
56.9
作者：
Servant, G;Weiner, OD;Bourne, HR
通讯作者：
Bourne, HR