Cell Biology of Nutrient Regulated Gene Expression

The analysis of regulated gene expression remains a substantial challenge in contemporary biology, and deciphering the entire repertoire of signaling mechanisms is necessary to fully understand how eukaryotic cells properly control their growth and development. Yeast and mammalian cells respond to the presence of low levels of extracellular amino acids by enhancing amino acid uptake, thus amino acids induce their own uptake. We are studying the molecular mechanisms underlying this process in the yeast Saccharomyces cerevisiae. The use of yeast has allowed us to rationally investigate the mechanisms of signal transduction in great detail. We have defined the key signaling events that define the SPS-sensing pathway, and have achieved a general understanding of how this pathway transmits amino acid induced signals from the plasma membrane to the promoters of responsive genes. Our studies have illuminated several novel aspects of eukaryotic-specific gene regulation, including receptor-activated proteolysis of latently expressed transcription factors, and transcriptional repression by integral components of the inner nuclear membrane.

Additionally our work has revealed the existence of membrane-localized chaperones that function in the endoplasmic reticulum to prevent inappropriate molecular interactions between hydrophobic segments of polytopic membrane proteins as they insert into the membrane. Although these findings are in seemingly disparate areas of research, i.e., signal transduction vs. membrane protein biogenesis, our results are in fact highly interrelated. The major amino acid sensor and signaling component in the plasma membrane, and the proteins catalyzing amino acid uptake are polytopic membrane proteins that require the same membrane-localized chaperone to be functional expressed. Our results provide an obvious example that to fully understand cellular signaling systems requires a broad understanding of cell biology. Based on our understanding of amino acid sensing mechanisms in yeast, we have examined whether similar mechanisms operate in Candida albicans, the most common human fungal pathogen. Our results indicate that C. albicans cells do indeed sense and respond to extracellular amino acids in a manner that is remarkably similar to yeast cells, and their ability to do so is important for virulent growth.

For further information regarding the major topics being addressed in our laboratory, please follow the project link to the left.
 

Keywords

Saccharomyces cerevisiae, Candida albicans, nutrient sensing, polytopic membrane protein biogenesis, transcription

Selected publications

Omnus, D.J., & Ljungdahl, P.O. (2013). Rts1-protein phosphatase 2A antagonizes Ptr3-mediated activation of the signaling protease Ssy5 by casein kinase I. Mol. Biol. Cell. (Epub ahead of print)

Omnus, D.J., Pfirrmann, T., Andréasson, C. and Ljungdahl, P.O. (2011). A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5. Mol Biol Cell. 22:2754-65

Davis, M.M., Alvarez, F.J., Ryman, K., Holm, Å.A., Ljungdahl, P.O. and Engström, Y. (2011). Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans. PLoS ONE. 6:e27434

Kota, J., Gilstring, C.F. and Ljungdahl, P.O. (2007). Membrane chaperone Shr3 assists in folding amino acid permeases preventing precocious ERAD. J Cell Biol. 176:617-28

Boban, M., Zargari, A., Andréasson, C., Heessen, S., Thyberg, J. and Ljungdahl, P.O. (2006). Asi1 is an inner nuclear membrane protein that restricts promoter access of two latent transcription factors. J Cell Biol. 173:695-707