Phosphatidylinositol 4-kinase III beta regulates cell shape, migration, and focal adhesion number.
Phosphatidylinositol 4-kinase III beta regulates cell shape, migration, and focal adhesion number.
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DOI：
10.1091/mbc.e19-11-0600
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发表时间：
2020-08-01
影响因子：
3.3
通讯作者：
Lee JM
中科院分区：
文献类型：
--
作者：
Bilodeau P;Jacobsen D;Law-Vinh D;Lee JM
细胞形状受细胞粘附、细胞骨架和膜动力学调节。细胞形状、粘附和运动性具有复杂的关系，理解它们对于理解发育模式和胚胎发生是重要的。在这里，我们表明，脂质激酶磷脂酰肌醇4-激酶III β（PI 4KIII β）调节细胞的形状，迁移和粘着斑（FA）的数量。PI 4KIII β从磷脂酰肌醇产生磷脂酰肌醇4-磷酸（PI 4P），并在一部分人乳腺癌中高度表达。PI 4KIII β及其产生的PI 4P调节多种细胞功能，包括控制高尔基体结构、苍蝇生育力和Akt信号传导。在这里，我们发现PI 4KIII β表达的缺失减少了细胞迁移并改变了NIH 3 T3成纤维细胞的细胞形状。这些变化伴随着缺乏PI 4KIII β的细胞中FA数量的增加。此外，我们发现，含有PI 4P的囊泡在迁移过程中移动到迁移的前沿，其中一些囊泡拴系并与FA融合。融合与FA分解相关。这表明PI 4KIII β和PI 4P在细胞粘附和细胞形状维持中的新的调节作用。
Cell shape is regulated by cell adhesion and cytoskeletal and membrane dynamics. Cell shape, adhesion, and motility have a complex relationship and understanding them is important in understanding developmental patterning and embryogenesis. Here we show that the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIIIβ) regulates cell shape, migration, and focal adhesion (FA) number. PI4KIIIβ generates phosphatidylinositol 4-phosphate (PI4P) from phosphatidylinositol and is highly expressed in a subset of human breast cancers. PI4KIIIβ and the PI4P it generates regulate a variety of cellular functions, ranging from control of Golgi structure, fly fertility, and Akt signaling. Here, we show that loss of PI4KIIIβ expression decreases cell migration and alters cell shape in NIH3T3 fibroblasts. The changes are accompanied by an increase in the number of FA in cells lacking PI4KIIIβ. Furthermore, we find that PI4P-containing vesicles move to the migratory leading edge during migration and that some of these vesicles tether to and fuse with FA. Fusion is associated with FA disassembly. This suggests a novel regulatory role for PI4KIIIβ and PI4P in cell adhesion and cell shape maintenance.