The Target of Rapamycin pathway in Photoautotrophic organisms
Cell proliferation and cell growth are two central aspects of every living organism. The control of these processes involves a number of complex signal transduction pathways, which as a consequence of their importance have to be tightly regulated. One of the central regulatory pathways is controlled by the Target of Rapamycin (TOR).
TOR translates environmental and nutritional information into permissive or restrictive growth decisions. TOR, which is highly conserved throughout the whole eukaryotic kingdom, is a modular, 270 kDa serine/threonine kinase from the phosphatidylinositol kinase-related kinase family.
In non-photosynthetic organisms, TOR has been shown to nucleate two structurally and functionally independent complexes (TORC1 and TORC2). It is very likely that only TORC1 is available in plant cells. Recent studies in Arabidopsis and Tobacco have clearly demonstrated that the TOR-pathway regulates protein synthesis and protein degradation, in dependence of the activation state of TOR.
A major advantage in elucidating the role and function of TOR was the fact that TOR was specifically, inhibited by a polycyclic antifungal metabolite of Streptomyces hygroscopicus, namely the macroyclic lactone rapamycin. The situation of having an essential protein and a specific inhibitor at the same time was a quite unique scenario and accelerated the progress in the field of human, yeast and drosophila TOR research. The rapamycin-based studies uncovered more and more novel functions of TOR, including a wide range of cellular processes, like transcription, translation, ribosome biogenesis, cell-cycle, cytoskeleton organization, autophagy and regulation (activation and repression) of distinct metabolic processes.
Unfortunately, even though many of the TOR-pathway genes including up and downstream regulators like S6K, PDK1, RPS6, and PP2A are highly conserved in photoautotrophic organisms, the research in plants is still lacking far behind the well-studied human and yeast model organisms. This delay comes from the fact that plants are largely insensitive to rapamycin, making the research much more tedious. A recently discovered possibility for the analysis of the TOR function in a photoautotrophic organism is offered by the green algae Chlamydomonas reinhardtii, which in contrast to higher plants displays rapamycin sensitivity. Due to its relatively simple cultivation conditions, the possibility to synchronize the cells and the fact that Chlamydomonas has a sequenced genome, this photosynthetic organism could possibly become the “green yeast” for plant-related TOR research.
An additional complication in studying TOR-function in plants, but also non-photosynthetic organisms, comes from the fact that loss of function of most of the TOR-pathway genes leads to embryo lethality. Therefore, genetic studies have to rely on inducible knock-out, using e.g. artificial micro (ami) or small interfering (si)RNAs, which provides a viable option to study the function of essential TOR-pathway genes like TOR, Raptor, S6K or TCTP.