Type Iγ PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis
Type Iγ PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis
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DOI：
10.1091/mbc.e07-05-0428
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发表时间：
2007-12-01
影响因子：
3.3
通讯作者：
Huttenlocher, Anna
中科院分区：
文献类型：
--
作者：
Lokuta, Mary A.;Senetar, Melissa A.;Huttenlocher, Anna
细胞极化对于定向迁移和白细胞募集到发炎组织是必要的。最近在定义趋化过程中调节趋化剂诱导的细胞极性的分子机制方面取得了进展，包括磷酸肌醇 3-激酶 (PI3K) 依赖性磷脂酰肌醇 (3,4,5)-三磷酸 [PtdIns(3,4,5)P-3] 在前沿合成的贡献。然而，人们对细胞后部的分子组成以及尾足在细胞运动过程中如何发挥作用知之甚少。在这里，我们证明，产生 PtdIns(4,5)P-2 的磷脂酰肌醇磷酸激酶 I gamma (PIPKI gamma 661) 在原代中性粒细胞和分化的 HL-60 细胞 (dHL-60) 趋化过程中在尾足中富集。使用延时显微镜，我们发现 PIPKI gamma 661 在细胞后部的富集发生在趋化剂刺激的早期，并且在趋化过程中持续存在。因此，我们能够在趋化过程中检测到尾足中 PtdIns(4,5)P2 的富集。激酶死亡的 PIPKI gamma 661 的过度表达会损害尾足形成和后部回缩，这与 ROCK 信号传导的抑制类似，表明 PtdIns(4,5)p(2) 合成对于在趋化过程中引发后背反应非常重要。总之，我们的研究结果确定了 PIPKI gamma 661 的一个先前未知的功能，作为在趋化过程中调节后回缩的背部信号的新成分。
Cell polarization is necessary for directed migration and leukocyte recruitment to inflamed tissues. Recent progress has been made in defining the molecular mechanisms that regulate chemoattractant-induced cell polarity during chemotaxis, including the contribution of phosphoinositide 3-kinase (PI3K)-dependent phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P-3] synthesis at-the leading edge. However, less is known about the molecular composition of the cell rear and how the uropod functions during cell motility. Here, we demonstrate that phosphatidylinositol phosphate kinase type I gamma (PIPKI gamma 661), which generates PtdIns(4,5)P-2, is enriched in the uropod during chemotaxis of primary neutrophils and differentiated HL-60 cells (dHL-60). Using time-lapse microscopy, we show that enrichment of PIPKI gamma 661 at the cell rear occurs early upon chemoattractant stimulation and is persistent during chemotaxis. Accordingly, we were able to detect enrichment of PtdIns(4,5)P2 at the uropod during chemotaxis. Overexpression of kinase-dead PIPKI gamma 661 compromised uropod formation and rear retraction similar to inhibition of ROCK signaling, suggesting that PtdIns(4,5)p(2) synthesis is important to elicit the backness response during chemotaxis. Together, our findings identify a previously unknown function for PIPKI gamma 661 as a novel component of the backness signal that regulates rear retraction during chemotaxis.