COP9 complex maintains neuroblast growth and proliferation by regulating Akt/mTor pathway
Nandan Jayaram, Priyanka PandeyiD, Syed Arjimand, Deepa Balasubramanian, Manish JaiswaliD, Sonal Nagarkar-JaiswaliD
Abstract
The nervous system consists of the brain and associated structures that are replete with highly specialised neurons and glia. Central to the development of the brain are Neural Stem Cells, which self-renew to maintain their number and also give rise to differentiated progeny. To identify genes involved in the maintenance of Drosophila neural stem cells, neuroblasts, we performed a protein expression screen followed by a protein knockdown screen using deGradFP system. Through this, we identified CSN7, a COP9 signalosome (CSN) subunit, which is enriched in neuroblasts and essential for neural development. CSN is a highly conserved multi-protein complex that regulates proteasome-mediated protein degradation via modulation of Cullin-RING E3 ligases. We found that loss of CSN7 and CSN1b lead to a decrease in neuroblast size and a reduced mitotic index. Our results show that CSN7/CSN1b regulates Akt-TOR signalling in the developing larval brain. Furthermore, we found that this regulation is mediated by Cul1. Overall, our work describes a hitherto undescribed role for the components of the CSN complex in neural development.
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