HSP83/HSP90 PROMOTES DROSOPHILA NEURAL STEM CELL REACTIVATION THROUGH PHYSICAL ASSOCIATION WITH INR

Abstract

Stem cells switch between quiescence and proliferation to maintain tissue homeostasis. In Drosophila larval brains, insulin receptor (InR)/PI3K/Akt pathway triggers neural stem cells (NSCs) to exit from quiescence (reactivation). However, intrinsic mechanisms that control the InR/PI3K/Akt pathway during NSC reactivation remain unknown. Here, we have identified Heat shock protein 83 (Hsp83/Hsp90), a molecular chaperone, as a novel intrinsic regulator of NSC reactivation. Hsp83 and its co-chaperone Cdc37, but not seven HSp70 isoforms, are crucial for NSC reactivation. Remarkably, Hsp83 overexpression is sufficient to trigger premature reactivation of NSCs. Both Hsp83 and Cdc37 physically associate with InR and are required for the activation of InR pathway. Finally, reactivation defects observed in hsp83-depleted brains were rescued by over-activation of the InR/PI3K/Akt pathway, suggesting that Hsp83 acts upstream of the InR/PI3K/Akt pathway to promote NSC reactivation. Our study has revealed a novel intrinsic mechanism that activates InR pathway to promote NSC reactivation.