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The Ion Transporter NKCC1 Links Cell Volume to Cell Mass Regulation by Suppressing mTORC1.

Cell Rep. 2019-05; 
DemianWael L,PersaudAvinash,JiangChong,Coyaudétienne,LiuShixuan,KapusAndras,KafriRan,RaughtBrian,RotinDan
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摘要

mTORC1 regulates cellular growth and is activated by growth factors and by essential amino acids such as Leu. Leu enters cells via the Leu transporter LAT1-4F2hc (LAT1). Here we show that the Na/K/2Cl cotransporter NKCC1 (SLC12A2), a known regulator of cell volume, is present in complex with LAT1. We further show that NKCC1 depletion or deletion enhances LAT1 activity, as well as activation of?Akt and Erk, leading to activation of mTORC1 in cells, colonic organoids, and mouse colon. Moreover, NKCC1 depletion reduces intracellular Na concentration and cell volume (size) and mass and stimulates cell proliferation. NKCC1, therefore, suppresses mTORC1 by inhibiting its key activating signaling pat... More

关键词

Gln transporter,LAT1-4F2hc,Leu transporter,SLC12A2,SLC7A5-SLC3A2,cell mass,cell volume,mT