Sungki Hong

Abstract mTORC1 is a central regulator of cell growth that is directly activated by the small GTPase Rheb on the lysosomal membrane in response to growth factors. We recently reported that polyubiquitinated Rheb facilitates its interaction with mTORC1, leading to mTORC1 activation. However, the molecular mechanisms underlying the ubiquitination of Rheb and its interaction with mTORC1 for activation are not fully understood.

Highlights • Amino acids stimulate mTORC1 activity in part by enhancing Rheb ubiquitination • Polyubiquitinated Rheb displays a strong binding preference for mTORC1 • ATXN3 interacts with and deubiquitinates Rheb on the lysosome • Inactive Rags recruit ATXN3 to the lysosome upon amino acid starvation Summary Amino-acid-induced lysosomal mechanistic target of rapamycin complex 1 (mTORC1) localization through the Rag GTPases is a critical step for its activation by Rheb GTPase.

The natural rate of interest is the real short-term rate that supports an economy operating at its potential output without increasing inflation. It is an essential benchmark rate for policymakers who determine the policy rate. If potential output declines, the natural rate declines with it. However, we do not directly observe the natural rate.