Lin’s paper got a News & Views and Editor’s Choice at Science
May 2, 2019
Rag GTPases play a crucial role in mTORC1 activation by promoting its recruitment to the lysosomal surface in a nutrient-dependent manner. A study now identifies a family of lysosomal G-protein-coupled receptors as modulators of Rag GTPases localization and activation, adding one more component to the fast-growing mTOR regulatory network.
The mammalian target of rapamycin complex 1 (mTORC1) protein kinase is activated at the lysosomal membrane and helps control autophagy and metabolism. It interacts with other proteins that act as sensors for stimuli like amino acids. Gan et al. used an unbiased screen to discover another protein that functions in this complex, one with similarity to heterotrimeric G protein—coupled receptors (GPCRs). The GPCR-like protein, GPR137B, appears to regulate cycles of association and release of the small guanosine triphosphatase Rag and mTORC1 at the lysosome even in the absence of amino acids. Whether a ligand for the orphan receptor could provide additional regulation adds a further intriguing twist.