Stress granule proteins as integrators of metabolic signals at the lysosomes

Ulrike Rehbein, Kathrin Thedieck

The tuberous sclerosis protein (TSC) complex acts as a relay for anabolic signaling and as a tumor suppressor. These functions are mediated via the inhibition of the metabolic master regulator mTORC1 (mechanistic target of rapamycin complex 1) at its central signaling platform – the lysosomes. We recently discovered that the stress granule protein G3BP1 (Ras GTPase-activating protein-binding protein 1) anchors the TSC complex to lysosomes needed for the suppression of mTORC1 by nutritional signals (PMID: 33497611). Using biochemical approaches and in silico predictions we find that the G3BP1-TSC axis mediates metabolic signals to mTORC1, suggesting a novel mode of TSC-mediated nutrient sensing.