Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Mol Biol Cell. 2020 Aug 1;31(17):1904-1916. doi: 10.1091/mbc.E19-11-0600. Epub 2020 Jun 17.
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.
细胞形状受细胞黏附、细胞骨架和膜动力学的调节。细胞形状、黏附和运动之间存在复杂的关系，理解这些关系对于理解发育模式和胚胎发生至关重要。在这里，我们表明脂质激酶磷脂酰肌醇 4-激酶 IIIβ（PI4KIIIβ）调节细胞形状、迁移和焦点黏附（FA）数量。PI4KIIIβ 从磷脂酰肌醇生成磷脂酰肌醇 4-磷酸（PI4P），在人类乳腺癌的一部分中高度表达。PI4KIIIβ 和它生成的 PI4P 调节各种细胞功能，从控制高尔基体结构、果蝇生育能力和 Akt 信号传导。在这里，我们表明 PI4KIIIβ 表达的丧失会降低 NIH3T3 成纤维细胞的迁移并改变细胞形状。这些变化伴随着缺乏 PI4KIIIβ 的细胞中 FA 数量的增加。此外，我们发现含有 PI4P 的囊泡在迁移过程中移动到迁移的前沿，并且其中一些囊泡与 FA 连接并融合。融合与 FA 解组装相关。这表明 PI4KIIIβ 和 PI4P 在细胞黏附和细胞形状维持中具有新的调节作用。
