Abstract：
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.
摘要：
磷脂酰肌醇(PI)4,5-二磷酸(PIP2)参与许多生物学功能。然而,PIP2在集体细胞迁移中的机制仍然难以捉摸。本研究通过调节PIP2的不对称分布，强调了三磷酸胞苷合酶（CTPsyn）在集体边界细胞迁移中的调节作用。我们证明了含有突变CTPsyn细胞的边界细胞簇抑制了迁移。CTPsyn在果蝇边缘细胞簇的前缘与肌动蛋白共富集，其中PIP2富集，这种富集取决于CTPsyn的活性。在CTPsyn突变体与PI生物合成基因之间发现了边界细胞迁移的遗传相互作用。CTPsyn减少导致胞吞再循环的不对称活性丧失。此外，揭示了外囊复合体和CTPsyn突变体的成分之间的遗传相互作用，表明CTPsyn活性调节PIP2相关的不对称胞吐活性。此外，CTPsyn活性对于边缘细胞簇中的RTK极化分布至关重要。我们提出了一个模型，在该模型中，PIP2的不对称生成需要CTPsyn活性，以通过集体细胞迁移中的内吞再循环来丰富RTK信号传导。
