Novel links in the plant TOR kinase signaling network

Abstract

Nutrient and energy sensing and signaling mechanisms constitute the most ancient and fundamental regulatory networks to control growth and development in all life forms. The target of rapamycin (TOR) protein kinase is modulated by diverse nutrient, energy, hormone and stress inputs and plays a central role in regulating cell proliferation, growth, metabolism and stress responses from yeasts to plants and animals. Recent chemical, genetic, genomic and metabolomic analyses have enabled significant progress toward molecular understanding of the TOR signaling network in multicellular plants. This review discusses the applications of new chemical tools to probe plant TOR functions and highlights recent findings and predictions on TOR-mediate biological processes. Special focus is placed on novel and evolutionarily conserved TOR kinase effectors as positive and negative signaling regulators that control transcription, translation and metabolism to support cell proliferation, growth and maintenance from embryogenesis to senescence in the plant system.

Figure 1

Central roles of TOR in early embryogenesis, cell cycle control, and plant growth and development. The null tor mutants arrest at the 16–32 cell stage in early embryogenesis. Estradiol-inducible tor mutants block DNA synthesis in the root meristem, seedling development, and root hair growth. Fully differentiated leaf mesophyll cells maintain robust TOR kinase activity for S6K1-T449 phosphorylation that is sensitive to rapamycin without (upper panel) or with (lower panel) FKBP12 (F12) overexpression. Rap, rapamycin.

Figure 2

The multifaceted functions of TOR kinase are uncovered by integrated chemical, genetic, genomic and metabolomics analyses. The complex TOR signaling network contributes to the regulation of plant life from embryogenesis to senescence by integrating central and secondary carbon metabolism with bioenergetics, biosynthesis, signaling, chromatin modulators, transporters, autophagy and cell cycle regulation. RNAi, RNA interference; amiRNA, artificial microRNA; RP, ribosome protein; uORF, upstream open reading frame; HSP, heat shock protein; TCA, tricarboxylic acid cycle; ETC, mitochondria electron transport chain; AGP, arabinogalactan protein; TPS, trehalose-6-phosphate synthase; TAG, triacylglycerol; XTH, xyloglucan endotransglucosylase; CYP, cytochrome P450. Torin1,2, WYE354, KU63794, PP242 and AZD8055 are specific ATP-competitive chemical inhibitors of TOR kinase.

Figure 3

The plant TOR signaling network. Arabidopsis TOR kinase is modulate by diverse upstream inputs and regulatory partners (Raptor and LST8) to phosphorylate S6K1,2, TAP46, E2FA, E2FB, LIPIN and ATG1 in the nucleus, nucleolus and cytosol to control transcription, cell cycle, endocycle, rRNA transcription, ribosome biogenesis, translation and metabolism, all pivotal to cell proliferation and growth. S6K, small ribosome protein 6 (RPS6) kinase; TAP46, a regulatory subunit of PP2A; E2FA/B, transcription factors; RBR, retinoblastoma repressor; HD2B, histone deacetylase2B; eIF3h, eukaryotic translation initiation factor 3h; ATG1, autophagy related kinase1.