Mios-flox Mouse

Mios is a component of the GATOR2 complex, which is crucial for amino acids to activate mTORC1, a key regulator controlling growth by modulating anabolic and catabolic processes in response to environmental cues [1]. The GATOR2-GATOR1 signaling axis is essential for amino-acid-dependent mTORC1 activation [3]. In zebrafish, Rbpms2 promotes female fate upstream of Mios, integrating the regulation of sexual differentiation factors and nutritional availability pathways during oogenesis [2].

Disruption of the Ring domains of Mios completely impedes amino-acid-mediated mTORC1 activation. Mechanistically, the Ring domain of Mios acts as a hub to maintain GATOR2 integrity; its disruption leads to self-ubiquitination of WDR24. Physiologically, leucine stimulation dissociates Sestrin2 from the Ring domain of WDR24, contributing to GATOR2-mediated GATOR1 inactivation. WDR24 ablation or Ring deletion in mice, which can be considered as a form of loss-of-function, prevents mTORC1 activation, leading to severe growth defects and embryonic lethality at E10.5 [3].

In conclusion, Mios is essential for the proper function of the GATOR2 complex in the mTORC1 pathway, playing a key role in nutrient sensing and embryonic development. The loss-of-function experiments in mice highlight the significance of Mios in maintaining normal growth and development, and further suggest its potential implications in understanding related growth-and development-associated diseases.