TOR tour to auxin.

Auxin is a principal growth hormone in plants. A study by Schepetilnikov et al (2013) now reports that TOR is activated by auxin and regulates expression of auxinresponsive genes by facilitating translation reinitiation of mRNAs with uORFs at their 50 UTRs. In this way, TOR acts at the crossroad of the plasma membrane and nuclear auxin signalling pathways to link auxin with general nutrient signalling. Auxin signalling acts through concentration gradients to regulate developmental processes in plants and the flow of Auxin can be rapidly altered by environmental stimuli resulting in the redirection of plant growth. Auxin concentrations are read and translated into gradients of regulatory proteins, as seen for the PLETHORA (PLT) transcription factors, which determine cellular states, such as stem cell maintenance, cell proliferation, and cell elongation. The currently dominating view is that auxin is perceived by the nuclear TIR/AFB receptors, F-box proteins, which regulate turnover of the AUX/IAA transcriptional repressors to control gene transcription through a family of AUXIN RESPONSE FACTORs (ARFs; Figure 1; Hayashi, 2012). Schepetilnikov et al (2013) now show that auxin also controls the abundance of key regulators in a post-transcriptional manner involving selective protein translation. They report that auxin activates TARGET OF RAPAMICIN (TOR), the evolutionary conserved central growth regulator in yeast, plants, and animals. TOR is known to control protein translation through translation initiation in yeast and animals, but its role is less well understood in plants. It was previously shown that TOR acts through the p70 RIBOSOMAL S6 KINASE (S6K) (Mahfouz et al, 2006) and Schepetilnikov et al (2013) now find that polysomes form a platform for TOR-dependent phosphorylation and activation of S6K. Inactive S6K is associated with polysomes; when TOR becomes activated by auxin, it is recruited to polysomes, leading to the phosphorylation and subsequent dissociation of active S6K. S6K in turn regulates the selective translation of mRNAs containing cis-acting regulatory sequences in the 50 untranslated region (50UTR). These sequences are short untranslated open reading frames (uORFs) that disrupt translation when ribosomes cannot reinitiate. The presence of uORFs in around 30% of Arabidopsis mRNAs indicates that this type of translational control is abundantly used in plants, and includes mRNAs in functional categories of hormone responses, sugar signalling, and cell-cycle control (Kim et al, 2007). Translation initiation factors (eIFs) can remain associated with the elongating ribosomes downstream of the uORFs to enable reinitiation (Roy et al, 2010). In animal cells, the eIF3 complex serves as a docking site for phosphorylation and activation of inactive S6K by TOR (Holz et al, 2005). Schepetilnikov et al (2013) show Arabidopsis S6K to phosphorylate eIF3h in a TOR-dependent manner leading to polysome loading of eIF3 and effective translation reinitiation of uORF-containing mRNAs in response to auxin. The regulation of translation reinitiation appears to be a principal component of the auxin response pathway, as plants depleted of TOR or expressing mutant eif3h display typical auxin-response phenotypes, such as altered root gravitropism (Figure 1B). How auxin signalling activates TOR is unclear at present but candidates for linking the two pathways exist. Early auxin responses are signalled through the AUXIN BINDING PROTEIN 1 (ABP1) located at the extracellular face of the plasma membrane (PM) in the cell wall (CW) and numerous rapid auxin responses are attributed to ABP1, including the potassium uptake, cell expansion, cytoskeletal formation and cellular polarisation (Sauer and Kleine-Vehn, 2011). Phospholipase D zeta2 (PLDz2) was shown to be required for auxin responses, but it is not clear whether this is signalled via ABP1 (Li and Xue, 2007). PLDs produce the signalling lipid second messenger, phosphatidic acid (PA) that in plants activates the PHOSPHOLIPID-DEPENDENT PROTEIN KINASE 1 (PDK1) (Anthony et al, 2004). PDK1 is a T-loop activator of a family of protein kinases, collectively known as AGC kinases, including S6K and PINOID (PID), the later regulating the polar localisation of the auxin efflux proteins, PINs. S6K is a convergence point between PDK1 and TOR signalling pathways, as S6K activation also depends on a conserved regulatory phosphorylation by TOR at its C-terminus. In animal cells, growth factors such as insulin connect to TOR through PDK1, AKT, and TSC1/TSC2, while the availability of sugars is signalled through AMP-activated kinase (AMPK). While plants lack TSC1/2 orthologues, it is becoming evident that TOR integrates cellular growth with availability of growth factors and nutrients in both plants and animals. Growth and cell proliferation are connected by selective translation of key cell-cycle regulators like the G1-specific cyclins (CYCDs). The protein abundance of the plant The EMBO Journal (2013) 32, 1069–1071 www.embojournal.org