Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Development. 2022 Aug 15;149(16). doi: 10.1242/dev.200190. Epub 2022 Aug 22.
Phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) is involved in many biological functions. However, the mechanisms of PIP2 in collective cell migration remain elusive. This study highlights the regulatory role of cytidine triphosphate synthase (CTPsyn) in collective border cell migration through regulating the asymmetrical distribution of PIP2. We demonstrated that border cell clusters containing mutant CTPsyn cells suppressed migration. CTPsyn was co-enriched with Actin at the leading edge of the Drosophila border cell cluster where PIP2 was enriched, and this enrichment depended on the CTPsyn activity. Genetic interactions of border cell migration were found between CTPsyn mutant and genes in PI biosynthesis. The CTPsyn reduction resulted in loss of the asymmetric activity of endocytosis recycling. Also, genetic interactions were revealed between components of the exocyst complex and CTPsyn mutant, indicating that CTPsyn activity regulates the PIP2-related asymmetrical exocytosis activity. Furthermore, CTPsyn activity is essential for RTK-polarized distribution in the border cell cluster. We propose a model in which CTPsyn activity is required for the asymmetrical generation of PIP2 to enrich RTK signaling through endocytic recycling in collective cell migration.
磷脂酰肌醇（PI）4,5-二磷酸（PIP2）参与许多生物功能。然而，PIP2 在细胞集体迁移中的作用机制仍不清楚。本研究通过调控 PIP2 的不对称分布，强调了胞嘧啶三磷酸合酶（CTPsyn）在集体边缘细胞迁移中的调节作用。我们发现，含有突变 CTPsyn 细胞的边缘细胞簇抑制了迁移。CTPsyn 与肌动蛋白一起在富含 PIP2 的果蝇边缘细胞簇的前缘富集，这种富集依赖于 CTPsyn 的活性。CTPsyn 突变与 PI 生物合成基因之间存在边缘细胞迁移的遗传相互作用。CTPsyn 的减少导致内吞再循环的不对称活性丧失。此外，外核蛋白复合物的组成部分与 CTPsyn 突变体之间也存在遗传相互作用，表明 CTPsyn 活性调节与 PIP2 相关的不对称胞吐作用。此外，CTPsyn 活性对于 RTK 在边缘细胞簇中的极化分布是必需的。我们提出了一个模型，其中 CTPsyn 活性对于不对称产生 PIP2 以通过集体细胞迁移中的内吞再循环富集 RTK 信号是必需的。
