Evolutionary Conservation of the Components in the TOR Signaling Pathways

Abstract

Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that controls multiple cellular processes upon various intracellular and extracellular stimuli. Since its first discovery, extensive studies have been conducted both in yeast and animal species including humans. Those studies have revealed that TOR forms two structurally and physiologically distinct protein complexes; TOR complex 1 (TORC1) is ubiquitous among eukaryotes including animals, yeast, protozoa, and plants, while TOR complex 2 (TORC2) is conserved in diverse eukaryotic species other than plants. The studies have also identified two crucial regulators of mammalian TORC1 (mTORC1), Ras homolog enriched in brain (RHEB) and RAG GTPases. Of these, RAG regulates TORC1 in yeast as well and is conserved among eukaryotes with the green algae and land plants as apparent exceptions. RHEB is present in various eukaryotes but sporadically missing in multiple taxa. RHEB, in the budding yeast Saccharomyces cerevisiae, appears to be extremely divergent with concomitant loss of its function as a TORC1 regulator. In this review, we summarize the evolutionarily conserved functions of the key regulatory subunits of TORC1 and TORC2, namely RAPTOR, RICTOR, and SIN1. We also delve into the evolutionary conservation of RHEB and RAG and discuss the conserved roles of these GTPases in regulating TORC1.

Phosphorylation by the stress-activated MAPK Slt2 down-regulates the yeast TOR complex 2

“…However, the model proposed was that, under appropriate stress conditions (including hypotonic shock and sphingolipid depletion), Slm1/2 dissociate from eisosomes, bind Ypk1, and deliver this substrate to the TORC2 compartment (Berchtold et al 2012;Niles et al 2012). On the other hand, equally compelling data demonstrate that it is the CRIM element present in Avo1 and its orthologs in fission yeast (Sin1) and mammalian cells (mSIN1) that binds and presents substrates to the catalytic center in TORC2 (Liao and Chen 2012;Tatebe and Shiozaki 2017).…”

Reciprocal regulation of photosynthesis and mitochondrial respiration by TOR kinase in Chlamydomonas reinhardtii

“…In most land plants, chlorophytes and rhodophytes, no RICTOR ortholog has been found suggesting that only TORC1 is conserved (Shi, Wu, & Sheen, 2018;Tatebe & Shiozaki, 2017;Wu et al, 2019).…”

Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

“…We further explored this relationship between the requirement for SKN-1 and MOM-2 by testing other candidate genes implicated in endoderm development [68–70]. We found that loss of RICT-1, the C. elegans orthologue of the human RICTOR (Rapamycin-insensitive companion of mTOR; [71]), a component of the TORC2 complex, which has been shown to antagonize SKN-1 function [68], results in opposite effects on skn-1(-) and mom-2(-) mutants (Fig. 8A).…”