The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function

• DOI: 10.1371/journal.pgen.1006036
• Publication Date: 2016-05-11T17:46:58Z
• Authors: Weili Cai; Youheng Wei; Michal Jarnik; John Reich; Mary A. Lilly
• Keywords: Genetic screen

TORC1 is a master regulator of metabolism in eukaryotes that responds to multiple upstream signaling pathways. The GATOR complex newly defined contains two sub-complexes, GATOR1, which inhibits activity response amino acid starvation and GATOR2, opposes the GATOR1. While GATOR1 has been implicated wide array human pathologies including cancer hereditary forms epilepsy, vivo relevance GATOR2 remains poorly understood metazoans. Here we define role component Wdr24 Drosophila. Using combination genetic, biochemical, cell biological techniques demonstrate both dependent independent functions regulation cellular metabolism. Through characterization null allele, show critical effector promotes robust activation growth broad Drosophila tissues. Additionally, epistasis analysis between wdr24 genes encode components revealed second function, lysosome dynamics autophagic flux. Notably, find additional members complex, Mio Seh1, also have function. These findings represent surprising previously unrecognized function lysosomes. Consistent with our Drosophila, through wdr24-/- knockout HeLa line determined acidification flux mammalian cells. Taken together data support model key required for