Slc38a9-flox Mouse

Slc38a9, a lysosomal membrane protein homologous to amino acid transporters, is also known as a transceptor [4]. It plays a crucial role in amino acid homeostasis and is an essential component in the mTORC1 signaling pathway. mTORC1, a master growth regulator, senses various environmental cues including amino acids, and SLC38A9 is required for arginine-mediated activation of mTORC1 [1]. It also mediates the transport of many essential amino acids out of lysosomes in an arginine-regulated manner, which is vital for cell growth [1].

In zebrafish, slc38a9 -/- mutants showed increased apoptosis, dysregulated amino acid metabolism, and glycolysis/gluconeogenesis disorders [3]. A quarter of the mutant embryos developed pericardial edema and died prematurely. These findings suggest that Slc38a9 is indispensable for embryonic development, metabolic regulation, and stress adaption [3]. In pancreatic cancer cells, which rely on macropinocytosed protein as a nutrient source, SLC38A9 is required to form tumors, indicating its role in cancer-related metabolic processes [1]. Also, SLC38A9 knockdown prevents S1-induced endolysosome de-acidification and blocks the S protein-mediated entry of pseudo-SARS-CoV-2 in multiple cell lines, revealing its function in regulating viral entry [2].

In conclusion, Slc38a9 is essential for maintaining amino acid homeostasis and regulating the mTORC1 signaling pathway. Model-based research, such as the zebrafish slc38a9 knockout model, has revealed its crucial roles in embryonic development, metabolism, and disease-related processes like cancer growth and viral entry. Understanding the function of Slc38a9 provides insights into the mechanisms of these biological processes and potential therapeutic targets for related diseases.