Sci. STKE, 5 June 2007
Cell Metabolism Shore Up That Wall!
Nancy R. Gough
Science's STKE, AAAS, Washington, DC 20005, USA
Single-celled and multicellular organisms must control metabolic flux in response to changing cellular and organismal needs. For example, will glucose be used to create ATP, to synthesize glycogen, to generate NADPH, or to glycosylate lipids and proteins? Disruption of these processes underlies diseases such as diabetes and obesity. Smith and Rutter found a pathway in Saccharomyces cerevisiae controlling glucose partitioning from cell wall synthesis to glycogen storage. The kinases Psk1 and Psk2 (Psk1/2) phosphorylate UDP-glucose pyrophosphorylase (Ugp1), which is a key enzyme in producing UDP-glucose for either glycogen (energy storage) or glucan (cell wall synthesis). Yeast deficient in both Psk1 and Psk2 activity or expressing a mutant version of Ugp1 in which the phosphorylated serine is replaced by alanine (Ugp1-S11A) exhibit defective growth on galactose, increased glycogen content per cell, and decreased sensitivity to a toxin that binds to β-(1,6)-glucan. Although phosphorylation did not alter the catalytic activity of Ugp1, lack of Psk1/2 activity or expression of the Ugp1-S11A mutant resulted in the loss of one population of Ugp1. In wild-type yeast, there are two populations of Ugp1, corresponding to the phosphorylated (isoform 1) and the nonphosphorylated (isoform 2) forms that were readily separated by anion exchange chromatography, and these two forms exhibit differences in conformation based on their differences in sensitivity to proteases and different proteolysis profiles. Yeast that did not produce isoform 2 showed altered sensitivity to various chemicals that cause cell wall stress. The authors propose that phosphorylation alters the cellular distribution of Ugp1 from the cytosol (for glycogen synthesis) to the cell membrane (for cell wall synthesis). Forced localization of Ugp1 to the plasma membrane rescued the Psk1/2-deficient cells from inability to grow on galactose and reduced glycogen content and restored β-(1,6)-glucan content per cell to levels similar to those in wild-type yeast.
T. L. Smith, J. Rutter, Regulation of glucose partitioning by PAS kinase and Ugp1 phosphorylation. Mol. Cell 26, 491-499 (2007). [PubMed]
Citation: N. R. Gough, Shore Up That Wall! Sci. STKE 2007, tw194 (2007).
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