The amino acid transporter SLC38A9 is a key component of a lysosomal membrane complex that signals arginine sufficiency to mTORC1
| Autor: | Shuyu, Wang, Zhi-Yang, Tsun, Rachel L, Wolfson, Kuang, Shen, Gregory A, Wyant, Molly E, Plovanich, Elizabeth D, Yuan, Tony D, Jones, Lynne, Chantranupong, William, Comb, Tim, Wang, Liron, Bar-Peled, Roberto, Zoncu, Christoph, Straub, Choah, Kim, Jiwon, Park, Bernardo L, Sabatini, David M, Sabatini |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Amino Acid Transport Systems
TOR Serine-Threonine Kinases Molecular Sequence Data Mechanistic Target of Rapamycin Complex 1 Arginine Article Protein Structure Tertiary HEK293 Cells Multiprotein Complexes Humans Amino Acid Sequence biological phenomena cell phenomena and immunity Lysosomes Monomeric GTP-Binding Proteins Signal Transduction |
| Popis: | The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine with a high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway. |
| Databáze: | OpenAIRE |
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