The GATOR2-GATOR1 signaling axis is essential for amino-acid-dependent mTORC1 activation. However, the molecular function of the GATOR2 complex remains unknown. Here, we report that disruption of the Ring domains of Mios, WDR24, or WDR59 completely impedes amino-acid-mediated mTORC1 activation. Mechanistically, via interacting with Ring domains of WDR59 and WDR24, the Ring domain of Mios acts as a hub to maintain GATOR2 integrity, disruption of which leads to self-ubiquitination of WDR24. Physiologically, leucine stimulation dissociates Sestrin2 from the Ring domain of WDR24 and confers its availability to UBE2D3 and subsequent ubiquitination of NPRL2, contributing to GATOR2-mediated GATOR1 inactivation. As such, WDR24 ablation or Ring deletion prevents mTORC1 activation, leading to severe growth defects and embryonic lethality at E10.5 in mice. Hence, our findings demonstrate that Ring domains are essential for GATOR2 to transmit amino acid availability to mTORC1 and further reveal the essentiality of nutrient sensing during embryonic development. [Display omitted] • Ring disruption in Mios, WDR24, and WDR59 impedes AA-mediated mTORC1 activation • Mios functions as a brake to prevent the self-ubiquitination of WDR24 • Leucine dissociates Sestrin2 from WDR24 Ring, leading to NPRL2 ubiquitination • Wdr24 deficiency prevents mTORC1 activation, leading to embryonic lethality in mice Ring domain of Mios acts as a hub to maintain GATOR2 integrity, disruption of which leads to self-ubiquitination of WDR24, while leucine stimulation potentiates the E3 ligase activity of WDR24 via impeding Sestrin2 binding to the Ring domain of WDR24 to confer its availability to the E2 enzyme UBE2D3 and subsequent ubiquitination of NPRL2, a process that is likely essential for leucine-dependent activation of mTORC1. [ABSTRACT FROM AUTHOR]