Target of Rapamycin kinase: central regulatory hub for plant growth and metabolism

The adaptation of plants to their environment requires tight regulation of metabolism and growth processes through central and highly connected signalling pathways. The signalling cascade involving the evolutionarily conserved Target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">Rapamycin(definition) (TOR) represents just such a central regulatory hub, and research on this protein kinase in plants has progressed significantly during the past decade. TOR is now firmly established as a central player in plant responses to the availability of nutrients such as sugars, stresses including those from pathogens, and hormones. Moreover plant-specific targets and regulators have recently been identified. The reviews in this special issue explore the various facets of regulation exerted by this fascinating kinase as well as its potential for crop improvement. Eukaryotic cells and organisms need to adjust basic processes such as cell division, growth and metabolism to the available resources and external conditions. These are sensed either directly, as in unicellular eukaryotes, or indirectly, for example through hormonal or nutrient signals, as occurs in multicellular organisms. Central to this regulation is the conserved kinase Target of Rapamycin (TOR), which has been shown to be a critical component of sensing mechanisms. The discovery of TOR is a perfect example of the serendipitous nature of research. It all started with the identification of a molecule produced by Streptomyces hygroscopicus, a bacterium isolated in the 1970s in a soil sample from the remote and mysterious Easter Island, known as Rapa Nui in Polynesian. This compound was thus named rapamycin (Vezina et al., 1975). Rapamycin was found to inhibit cell proliferation but the mechanism of action was unknown. It was only in the 1990s that Michael Hall’s group in Basel identified mutations in yeast which conferred resistance to rapamycin. This led to the seminal discovery of TOR, inhibition of which by rapamycin leads to arrested growth (Heitman et al., 1991; Montané and Menand, 2019). Michael Hall was later awarded the 2017 Lasker prize for medical research for this paramount discovery. TOR was subsequently identified in humans, where it was given the name mTOR (mammalian or mechanistic TOR), in various animals including flies and worms (Saxton et al., 2017; Mossmann et al., 2018), flowering plants (Menand et al., 2002) and algae (Perez-Perez et al., 2017). In all eukaryotes, TOR is a very large (around 250 kDa) serine/threonine kinase belonging to the phosphatidylinositol 3-kinase-related kinase (PIKK) family. Indeed, although TOR is a protein kinase, its catalytic domain is unconventional and resembles that of PI lipid kinases. Other members of this family include the conserved DNA damage checkpoint ataxia-telangiectasia mutated (ATM) and ATM-related (ATR) kinases, which are also present in plants. In yeast and animals, where TOR has been studied extensively, various upstream regulators and downstream effectors have been discovered, forming a complex and highly connected signalling pathway (Blenis, 2017). In these organisms ScTOR and mTOR play a major role in the regulation of cell growth and metabolism through the control of gene transcription, cell trafficking, insulin responses as well as protein synthesis and degradation. Therefore, TOR is involved in many human diseases including cancer and diabetes. Thorough biochemical work showed that TOR belongs to two very large complexes, TORC1 and TORC2, containing common and specific companion proteins (Wullschleger et al., 2006; Saxton et al., 2017; Mossmann et al., 2018). Structural models for TOR complexes are now available (Aylett et al., 2016; Karuppasamy et al., 2017). In plants only the TORC1 complex has been described so far which, together with TOR, comprises the evolutionarily conserved LST8 and RAPTOR proteins (Box 1). The conserved TOR (Target of Rapamycin) protein kinase acts in TORC1 (TOR complex 1) with LST8 and RAPTOR protein partners. This complex is found in all eukaryotes and is an important molecular element connecting nutrient, hormonal and stress signals to metabolism, growth and hormonal responses. TORC1 can be seen as a switch turning on anabolic and growth processes when conditions are favourable and inhibiting catabolism and nutrient recycling by autophagy(definition). TORC1 controls mRNA translation globally but also the translation of specific mRNAs such as those encoding proteins needed for stress or hormone responses. Mounting evidence suggest that TOR and SnRK1/2 (Snf1-related kinases) act in an opposing way and it has been shown that SnRKs inhibit TOR activity by phosphorylating the RAPTOR protein. In recent years, many targets of TOR have been identified in plants and algae including the ribosomal protein S6 kinase, the PP2A phosphatase partner TAP46, several components of the translation and cell division machinery, and also the PYL ABA receptors. HEAT, HEAT [Huntingtin, elongation factor 3 (EF3), protein phosphatase 2A (PP2A), TOR1] repeat domain involved in protein–protein interactions; FRB, FKBP12-rapamycin binding domain; KD, kinase domain. As in yeast and animals, TOR has been implicated in controlling plant growth and cell division (Caldana et al., 2019) and prominent inducers of TOR activity have been shown to be sucrose and glucose (Xiong et al., 2012; Dobrenel et al., 2016a; Shi et al., 2018). Indeed, a strong sugar–TOR growth-controlling axis has emerged from several studies in both roots and shoots (Xiong et al., 2013; Pfeiffer et al., 2016; Wu et al., 2019). Basically, sugars like sucrose and glucose strongly up-regulate TOR activity by a largely unknown mechanism and TOR activates meristems by inducing E2F and Wuschel transcription factors in root and shoot apical meristems, respectively (Xiong et al., 2013; Pfeiffer et al., 2016). Nutrient starvation or defects in nutrient assimilation also affect TOR activity. For example, a decrease in sulfur assimilation due to mutations in the sulfite reductase gen