Transmembrane 4 L Six Family Member 5 Senses Arginine for mTORC1 Signaling

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dc.contributor.authorJ W Jung-
dc.contributor.authorS J Y Macalino-
dc.contributor.authorM Cui-
dc.contributor.authorJ E Kim-
dc.contributor.authorH J Kim-
dc.contributor.authorD G Song-
dc.contributor.authorS H Nam-
dc.contributor.authorSemi Kim-
dc.contributor.authorS Choi-
dc.contributor.authorJ W Lee-
dc.date.accessioned2019-07-10T01:23:31Z-
dc.date.available2019-07-10T01:23:31Z-
dc.date.issued2019-
dc.identifier.issn15504131-
dc.identifier.uri10.1016/j.cmet.2019.03.005ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/18798-
dc.description.abstractThe mechanistic target of rapamycin complex (mTORC1) is a signaling hub on the lysosome surface, responding to lysosomal amino acids. Although arginine is metabolically important, the physiological arginine sensor that activates mTOR remains unclear. Here, we show that transmembrane 4 L six family member 5 (TM4SF5) translocates from plasma membrane to lysosome upon arginine sufficiency and senses arginine, culminating in mTORC1/S6K1 activation. TM4SF5 bound active mTOR upon arginine sufficiency and constitutively bound amino acid transporter SLC38A9. TM4SF5 binding to the cytosolic arginine sensor Castor1 decreased upon arginine sufficiency, thus allowing TM4SF5-mediated sensing of metabolic amino acids. TM4SF5 directly bound free L-arginine via its extracellular loop possibly for the efflux, being supported by mutant study and homology and molecular docking modeling. Therefore, we propose that lysosomal TM4SF5 senses and enables arginine efflux for mTORC1/S6K1 activation, and arginine-auxotroph in hepatocellular carcinoma may be targeted by blocking the arginine sensing using anti-TM4SF5 reagents. Lysosomal arginine is involved in mTORC1/S6K1 activation for cell growth. Jung et al. identify TM4SF5 as a membrane-based sensor of physiologic levels of arginine. TM4SF5 forms a complex with mTOR and the amino acid transporter SLC38A9 on lysosomal membranes in an arginine-regulated manner, leading to arginine efflux and mTOR/S6K1 activation.-
dc.publisherElsevier-Cell Press-
dc.titleTransmembrane 4 L Six Family Member 5 Senses Arginine for mTORC1 Signaling-
dc.title.alternativeTransmembrane 4 L Six Family Member 5 Senses Arginine for mTORC1 Signaling-
dc.typeArticle-
dc.citation.titleCell Metabolism-
dc.citation.number6-
dc.citation.endPage1319-
dc.citation.startPage1306-
dc.citation.volume29-
dc.contributor.affiliatedAuthorSemi Kim-
dc.contributor.alternativeName정재우-
dc.contributor.alternativeNameMacalino-
dc.contributor.alternativeNameCui-
dc.contributor.alternativeName김지언-
dc.contributor.alternativeName김혜진-
dc.contributor.alternativeName송대근-
dc.contributor.alternativeName남세희-
dc.contributor.alternativeName김세미-
dc.contributor.alternativeName최선-
dc.contributor.alternativeName이정원-
dc.identifier.bibliographicCitationCell Metabolism, vol. 29, no. 6, pp. 1306-1319-
dc.identifier.doi10.1016/j.cmet.2019.03.005-
dc.subject.keywordamino acid transporter-
dc.subject.keywordarginine sensor-
dc.subject.keywordhomology modeling-
dc.subject.keywordlysosome-
dc.subject.keywordmetabolism-
dc.subject.keywordmolecular docking modeling-
dc.subject.keywordmTOR-
dc.subject.keywordprotein interaction-
dc.subject.keywordtetraspanin trafficking-
dc.subject.keywordTM4SF5-
dc.subject.localamino acid transporter-
dc.subject.localarginine sensor-
dc.subject.localhomology modeling-
dc.subject.localHomology modeling-
dc.subject.locallysosome-
dc.subject.localmetabolism-
dc.subject.localMetabolism-
dc.subject.localmolecular docking modeling-
dc.subject.localmTOR-
dc.subject.localprotein interaction-
dc.subject.localProtein interaction-
dc.subject.localtetraspanin trafficking-
dc.subject.localTM4SF5-
dc.description.journalClassY-
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Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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