228B Poster - 01. Cell Stress and cell death
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Yingbiao Zhang; Chun-Yuan Ting; Shu Yang; Mary Lilly

Affiliation: National Institute of Child Health and Human Development, NIH, Bethesda, MD

Keywords:
h. other (nutrient stress); v. TOR

TORC1, a master regulator of metabolism, is dysregulated in a wide array of human diseases. The GATOR complex is an upstream regulator that controls the activation of TORC1 in response to nutrient stress. The GATOR complex is comprised of two subcomplexes, the GATOR1 complex (Iml1, Nprl2, Nprl3), inhibits TORC1 activity by serving as a GAP for the TORC1 activator RagA, a component of the lysosomally located Rag GTPase. Conversely, the GATOR2 complex opposes the activity of GATOR1, thus serving to promote TORC1 activity. Current models developed from studies in mammalian tissue culture cells suggest that the GATOR2 complex contains 5 components, Mio, Wdr24, Seh1, Sec13 and Wdr59, TORC1 activity is down regulated by loss function of any one of these components. In Drosophila, loss function mutants of mio, seh1 and wdr24 exhibit decreased TORC1 activity and cell growth in the female germline. Surprisingly, we find that deletion of the Wdr59 gene lead to the opposite phenotype. Specifically, wdr59 mutants have increased TORC1 activity and ovarian growth and decreased levels of autophagy. Our data support a model in which Wdr59 harbors neither GATOR2 nor GATOR1 function, but act as a positive regulator of GATOR1 by inhibiting the binding affinity of RagA to the GATOR1 complex in Drosophila germ cells.