Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proton-coupled amino acid transporter 1 (PAT1) is a transporter of amino acids in small intestinal enterocytes. PAT1 is, however, also capable of regulating cell growth and sensing the availability of amino acids in other cell types. The aim of the present study was to investigate the localization and function of PAT1 in smooth muscle cells (SMCs). The PAT1 protein was found in smooth muscles from rat intestine and in the embryonic rat aorta cell line A7r5. Immunolocalization and cellular fractionation studies revealed that the majority of the PAT1 protein located within the cell nucleus of A7r5 cells. These results were confirmed in primary SMCs derived from rat aorta and colon. A 3'-untranslated region of the PAT1 transcript directed the nuclear localization. Neither cellular starvation nor cell division altered the nuclear localization. In agreement, uptake studies of l-proline, a PAT1 substrate, in A7r5 cells suggested an alternative role for PAT1 in SMCs than in transport. To shed light on the function of PAT1 in A7r5 cells, experiments with downregulation of the PAT1 level by use of a siRNA approach were conducted. The growth rates of the cells were evaluated, and knockdown of PAT1 led to induced cellular growth, suggesting a role for PAT1 in regulating cellular proliferation of SMCs.
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PMID:PAT1 (SLC36A1) shows nuclear localization and affects growth of smooth muscle cells from rats. 2422 68

The lysosome-associated transporter proton-coupled amino acid transporter 1 (PAT1) promotes nutrient recycling through releasing luminal amino acids into the cytosol. Using HEK293 cells expressing an EGFP-tagged PAT1 (EGFP-PAT1) as a model, we identified a consensus tyrosine-based targeting signal in the cytosolic N-terminal region of PAT1, which facilitates its expression on the lysosome. Interestingly, this signal can be removed via protein cleavage in an amino acid-sensitive manner. The cleavage is suppressed upon amino acid starvation and is induced by amino acid replenishment. However, amino acid deficiency does not suppress the cleavage of amino acid-binding mutants of EGFP-PAT1. Our data support a mechanism, whereby amino acid binding induces PAT1 cleavage to remove a targeting signal, thus suppressing the expression of PAT1 on the lysosome.
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PMID:Amino acids suppress the expression of PAT1 on lysosomes via inducing the cleavage of a targeting signal. 2867 Jul 36

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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PMID:The amino acid transporter PAT1 regulates mTORC1 in a nutrient-sensitive manner that requires its transport activity. 3025 87