TORC1 spatial segregation and hysteresis are regulated by the small GTPase Arf1

Abstract

TORC1 is a central regulator of growth, integrating inputs from kinases and signaling proteins. How TORC1 activity is regulated, is still not completely understood. The small GTPase Arf1 has been implicated in TORC1 regulation, but the underlying mechanism remains elusive. Here, we show that Arf1 controls TORC1 in an allele-specific manner under nutrient and heat stress in yeast. Unexpectedly, both the hyperactive mutant arf1-11 and the loss-of-function mutant arf1-18 reduce TORC1 activity, while other loss-of-function alleles did not. We reveal two distinct functions of Arf1: first, it ensures Golgi-to-vacuole/lysosome transport for the functional maintenance of these organelles; second, it regulates TORC1 activity at the ER-Golgi-vacuole interface. Hyperactive Arf1-11 drives sequestration of Kog1 and Tor1 into cytoplasmic foci, to which Arf1-11 can be equally recruited. Importantly, Arf1 also promotes TORC1 re-activation during stress recovery - so-called hysteresis. Our data reveal an unexpected dual function for Arf1 as a negative and a positive regulator of TORC1 activity in a context-dependent manner. TeaserThe small GPTase Arf1 acts as a dual switch for the key cellular growth regulator TORC1 by increasing or decreasing TORC1 activity depending on nutritional status and stress.