The Drosophila Nprl2/Nprl3 complex controls the response to nutrient stress by modulating TORC1 activity

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NICHD	DEVBIO-8

* FARE Award Winner

Authors

• Y Wei
• MA Lilly

Abstract

Target of rapamycin complex 1 (TORC1) is master regulator to control cell growth and proliferation in eukaryotes. Recent studies have shown that Nitrogen permease regulators like 2 and 3 (Nprl2 and Nprl3) mediate an essential response to amino acid limitation upstream of TORC1. However, the precise role of Nprl2 and Nprl3 in metazoans remains poorly defined. We find that in the Drosophila female germline, Nprl2 and Nprl3 physically interact and target to lysosomes and autolysosomes, the sites of TORC1 activation. When females are starved for amino acids, young egg chambers keep intact but stop growing. Knocking down Nprl2 and Nprl3 in germline cells triggers young egg chambers apoptosis during starvation. Additionally, the recovery of female fertility is markedly delayed. Rapamycin, a TORC1 specific inhibitor, inhibits the young egg chamber apoptosis and the egg recovery defect in npr2/3 RNAi flies. Furthermore, knocking down Tsc1, a well-known TORC1 inhibitor, also causes the young egg chambers death. These results confirm that the young egg chamber death in nprl2/3 RNAi flies resulted from TORC1 hyperactivation during nutrient stress. Thus, our data suggest the presence of a metabolic checkpoint that initiates a cell death program when TORC1 activity inappropriately high during periods of nutrient scarcity.

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