Mechanistic target of rapamycin (mTOR) regulates extracellular trap production in clam Ruditapes philippinarum.

In the present study, a mechanistic target of rapamycin (RpmTOR) gene was identified and characterized in clam Ruditapes philippinarum and its role in extracellular traps (ETs) formation was investigated. Sequence and structural analyses showed that RpmTOR encodes a conserved mTOR family protein containing the characteristic DUF3385, FAT, FRB, PI3Kc, and FATC domains, and phylogenetic analysis clustered it with other molluscan mTOR homologs. RpmTOR is highly expressed in immune-related tissues and is significantly upregulated following infection with Vibrio parahaemolyticus. Functional experiments demonstrated that mTOR inhibition potentiated Lipopolysaccharide (LPS)-induced oxidative redox imbalance and enhanced ETs formation. Further investigations revealed that mTOR inhibition increased extracellular vesicles (EVs) output and altered EVs biophysical properties under LPS stimulation. Inhibiting EVs secretion partially attenuated ETs generation. In conclusion, these results suggest that mTOR may contribute to the modulation of ETs release in R. philippinarum, possibly through the regulation of oxidative factors and EV release-related processes.