Journal Article

Snf1/AMPK promotes the formation of Kog1/Raptor-bodies to increase the activation threshold of TORC1 in budding yeast

Luo, Xiangxia, Hughes Hallett, James E, Capaldi, Andrew P

2015

Overview

The target of rapamycin complex I (TORC1) regulates cell growth and metabolism in eukaryotes. Previous studies have shown that nitrogen and amino acid signals activate TORC1 via the small GTPases, Gtr1/2. However, little is known about the way that other nutrient signals are transmitted to TORC1. Here we report that glucose starvation triggers disassembly of TORC1, and movement of the key TORC1 component Kog1/Raptor to a single body near the edge of the vacuole. These events are driven by Snf1/AMPK-dependent phosphorylation of Kog1 at Ser 491/494 and two nearby prion-like motifs. Kog1-bodies then serve to increase the threshold for TORC1 activation in cells that have been starved for a significant period of time. Together, our data show that Kog1-bodies create hysteresis (memory) in the TORC1 pathway and help ensure that cells remain committed to a quiescent state under suboptimal conditions. We suggest that other protein bodies formed in starvation conditions have a similar function. In humans, yeast and other eukaryotes, a group of proteins called the Target of Rapamycin Complex I (TORC1) promote cell growth and increase metabolic activity when nutrients are plentiful. Previous studies have shown how molecules that contain the nutrient nitrogen – which is needed to make proteins – activate TORC1. However, it is not clear how other nutrients regulate this complex. Bakers yeast is a simple, single celled organism that researchers often use as a model to study how cells work. The yeast TORC1 is made up of three core proteins, including Kog1 and Tor1. Kog1 selectively recruits proteins to the complex, where they are modified by Tor1 to regulate their activity. Here, Hughes Hallett et al. used microscopy to study what effect sugar starvation has on the complex. In the experiments, yeast cells were genetically engineered so that Kog1 and Tor1 appeared fluorescent under the microscope. The experiments reveal that, when sugar is in short supply, Kog1 breaks away from the rest of the TORC1 and moves to another part of the cell where it accumulates to form a cluster called a “body”. This movement is driven by a “kinase” enzyme that adds chemical groups called phosphates to Kog1, and by regions within the Kog1 protein known as prion like domains. When sugar first becomes available again, Kog1 is still in the body so Tor1 cannot immediately trigger cell growth. However, once a steady supply of sugar resumes, Kog1 rejoins the rest of the complex and the cells start to grow. Together, Hughes Hallett et al.’s findings reveal that the formation of Kog1 bodies during sugar starvation creates a “memory” that prevents TORC1 from reactivating cell growth if sugar is only temporarily available. Humans have over 100 proteins that contain prion like domains. Therefore a future challenge is to find out whether any of these proteins form similar bodies that enable our cells to remember past events.

• Publisher: eLife Sciences Publications, Ltd,eLife Sciences Publications Ltd
• Subject: AMPK / Biochemistry / Computational and Systems Biology / prion / TORC1