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Research GBB Research Principal Investigators Prof. dr. Andreas Milias-Argeitis

Research Highlight

Prof. dr. Andreas Milias-Argeitis

Oscillatory localization dynamics of a TORC1 and PKA substrate (the Sfp1 transcription factor) during the yeast cell cycle. Figure taken from [2].
Oscillatory localization dynamics of a TORC1 and PKA substrate (the Sfp1 transcription factor) during the yeast cell cycle. Figure taken from [2].

Cell growth, the collection of processes through which cells accumulate biomass and increase in size, is essential for progression through the cell division cycle. The target of rapamycin (TOR) and protein kinase A (PKA) pathways are the two main, evolutionarily conserved regulators of cell growth in budding yeast, coupling carbon and nitrogen availability, internal metabolic signals and the presence of noxious stressors to several anabolic and catabolic processes that ultimately impact cell growth and division. Importantly, TOR complex 1 (TORC1) and PKA together regulate ribosome biogenesis and protein synthesis, two of the most resource-intensive anabolic process es that are necessary for biomass accumulation and cell cycle progression.

Motivated by our previous observations that protein synthesis rate dynamics drive cell cycle commitment in G1 [1], we sought to investigate whether the activities of TORC1 and/or PKA pathways also oscillate during the yeast cell cycle. Following TORC1 and PKA readouts using single-cell time-lapse microscopy of hundreds of diving cells, we observed that the activity of these pathways shows a maximum during G1 and a minimum at budding and late mitosis [2]. Analysis of mutants suggested that upstream nutrient-sensing regulators of TORC1 and PKA are part of the mechanism that generates the activity oscillations. Finally, single-cell observations of two fluorescently tagged ribosomal proteins showed that ribosomal protein synthesis displays strong oscillations which reflect the TORC1 and PKA activity pattern. Our findings demonstrated for the first time that the activity of these central growth control pathways is temporally organized and tightly coordinated with the cell cycle. This new aspect of TORC1 and PKA signaling will be important for understanding the full scope of cellular activities regulated by these pathways and the mechanisms that couple growth and cell cycle progression.

References:

[1] Litsios A, Huberts DH, Terpstra HM, ……, Exterkate M, Milias-Argeitis A* & Heinemann M* (2019) Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast. Nature Cell Biology 21(11): 1382-1392.

[2] Guerra P, Vuillemenot LAP, van Oppen YB, Been M & Milias-Argeitis A (2022) TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle. Journal of Cell Science 135(18): p.jcs260378

Last modified:20 October 2023 11.27 a.m.