Rraga-flox Mouse

RRAGA, which encodes Ras-related GTP-binding protein A (RagA), is a key player in the mTORC1 pathway [1,2,3,4,5,6]. RagA initially senses cellular amino acids (e.g., leucine) and controls mTORC1's translocation to the lysosomal membrane, a process crucial for cell growth regulation in response to various environmental cues such as nutrients, growth factors, and energy/oxygen status [1,6]. The mTORC1 pathway, in which RRAGA is involved, has far-reaching implications for cell growth and metabolism [4]. Genetic models, like gene knockout models, are valuable for studying RRAGA's functions.

A RRAGA knockout human iPSC line was generated using CRISPR/Cas9 technology, which may aid in developing new therapeutics for depression as RagA overexpression seems linked to depression onset [1]. In human lens epithelial cells, mutations in RRAGA associated with autosomal dominant cataracts disrupted mTORC1 signaling, including increased RRAGA relocation to lysosomes, up-regulated mTORC1 phosphorylation, down-regulated autophagy, and altered cell growth [5].

In summary, RRAGA is essential for the mTORC1-mediated amino acid sensing and cell growth regulation. Gene knockout models of RRAGA have provided insights into its role in conditions like depression and autosomal dominant cataracts, highlighting its potential as a therapeutic target in these disease areas.