The amino acid transporter PAT1 regulates mTORC1 in a nutrient-sensitive manner that requires its transport activity

氨基酸转运体 mTORC1型 运输机 细胞生物学 化学 生物 氨基酸 生物化学 营养感应
作者
Lingling Zhao,Xiangxiang Zhang,Xin Ji,Yaping Jin,Wei Liu
出处
期刊:Cellular Signalling [Elsevier]
卷期号:53: 59-67 被引量:5
标识
DOI:10.1016/j.cellsig.2018.09.017
摘要

The proton-coupled amino acid transporter PAT1 has been postulated to regulate the amino acid-stimulated mTORC1 through two different mechanisms, either it activates mTORC1 by sensing and transducing the lysosomal amino acid signal to mTORC1, or it inhibits mTORC1 by decreasing the signal level, as increased PAT1 has been shown to either activate or inactivate mTORC1 in the human embryonic kidney HEK293 cells. The current study aims to clarify the cause of these controversial observations, which is promoted by the recent discovery that the lysosomal PAT1 can be induced by starvation. Here, we show that under the normal culture condition, overexpression of PAT1 did not apparently change the mTORC1 activity in the fast proliferating cells. However when these cells were synchronized by starvation, followed by nutrient replenishment for a short period of time, the mTORC1 activity was decreased by PAT1 overexpression; if the nutrient stimulation lasted for longer time, the mTORC1 activities could be recovered in the PAT1-overexpressing cells. In addition, we showed the starvation-induced lysosomal PAT1 was gradually decreased during the nutrient replenishment. These results reveal that the influence of PAT1 on mTORC1 seems to be affected by the nutrient condition and the level of lysosomal PAT1. We further demonstrate that suppressing the transport activity of PAT1 abolished its inhibitory effect on mTORC1. Our data support a mechanism that PAT1 can negatively regulate mTORC1 by controlling the cellular nutrient signal level.
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