Drosophila CTP synthase regulates collective cell migration by controlling the polarized endocytic cycle

Phosphatidylinositol (PI) 4,5-bisphosphate (PI(4,5)P2 or PIP2) is involved in many biological functions. However, the mechanisms of PIP2 in collective cell migration remains 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 and 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, the CTPsyn activity is essential for RTK-polarized distribution in the border cell cluster. We propose a model that CTPsyn activity is required for the asymmetrical generation of PIP2 to enrich RTK signaling through endocytic recycling in collective cell migration.