Patronin/CAMSAP promotes reactivation and regeneration of Drosophila quiescent neural stem cells

The ability of stem cells to switch between quiescent and proliferative states is crucial for maintaining tissue homeostasis and regeneration. Drosophila quiescent neural stem cells (qNSCs) extend a primary protrusion that is enriched in acentrosomal microtubules and can be regenerated upon injury. Arf1 promotes microtubule growth, reactivation (exit from quiescence), and regeneration of qNSC protrusions upon injury. However, how Arf1 is regulated in qNSCs remains elusive. Here, we show that the microtubule minus‐end binding protein Patronin/CAMSAP promotes acentrosomal microtubule growth and quiescent NSC reactivation. Patronin is important for the localization of Arf1 at Golgi and physically associates with Arf1, preferentially with its GDP‐bound form. Patronin is also required for the regeneration of qNSC protrusion, likely via the regulation of microtubule growth. Finally, Patronin functions upstream of Arf1 and its effector Msps/XMAP215 to target the cell adhesion molecule E‐cadherin to NSC‐neuropil contact sites during NSC reactivation. Our findings reveal a novel link between Patronin/CAMSAP and Arf1 in the regulation of microtubule growth and NSC reactivation. A similar mechanism might apply to various microtubule‐dependent systems in mammals. Synopsis Drosophila Patronin promotes reactivation of quiescent neural stem cells (qNSCs) by regulating acentrosomal microtubule growth. It functions upstream of the Golgi‐resident small GTPase Arf1, and it is required for regeneration of the primary protrusion of qNSCs upon injury. Patronin/CAMSAP promotes acentrosomal microtubule growth in Drosophila qNSCs. Patronin promotes qNSC reactivation and regeneration of the primary protrusion upon injury. Patronin physically associates with and functions upstream of Arf1 during qNSC reactivation. Graphical Abstract Drosophila Patronin promotes reactivation of quiescent neural stem cells (qNSCs) by regulating acentrosomal microtubule growth. It functions upstream of the Golgi‐resident small GTPase Arf1, and it is required for regeneration of the primary protrusion of qNSCs upon injury.