Editors' ChoiceSTRESS SIGNALING

PKA Against P Bodies

Science Signaling  11 Oct 2011:
Vol. 4, Issue 194, pp. ec284
DOI: 10.1126/scisignal.4194ec284

Glucose deprivation causes the yeast Saccharomyces cerevisiae to enter a stationary phase and accumulate proteins and mRNAs in cytoplasmic foci called P bodies, which are thought to store these macromolecules until needed. Glucose stimulates the activity of the cyclic adenosine monophosphate–dependent protein kinase (PKA) in S. cerevisiae, leading Ramachandran et al. to investigate the role of this kinase in P body assembly. Genetic manipulations that increased PKA activity, such as expression of an allele encoding a mutant form of an upstream activator (RAS2val19), resulted in the formation of fewer P bodies in response to glucose deprivation. Conversely, genetic manipulations that decreased PKA activity resulted in P body formation in the presence of glucose. Pat1, a scaffold for P body assembly that is also involved in repressing translation and stimulating mRNA decay, was phosphorylated at Ser456 and Ser457 by PKA in vitro and in cells, and glucose starvation reduced phosphorylation of Pat1 at these residues. Expression of a Pat1 mutant that could not be phosphorylated by PKA (Pat1-AA) rescued the defect in P body formation caused by increased PKA signaling. A Pat1 mutant that mimicked the PKA-phosphorylated form (Pat1-EE) showed reduced association with Dhh1, which has roles in repressing translation and stimulating mRNA decay, and expression of this mutant reduced the amount of various P body proteins, including Dhh1, in these foci. S. cerevisiae with constitutive PKA activity, such as those expressing RAS2val19, do not enter the stationary phase and do not survive nutrient deprivation, and loss of viability in RAS2val19 stationary cultures was prevented by expression of Pat1-AA. Thus, phosphorylation of Pat1 by PKA may prevent P body assembly in cells experiencing nutrient-rich conditions.

V. Ramachandran, K. H. Shah, P. K. Herman, The cAMP-dependent protein kinase signaling pathway is a key regulator of P body foci formation. Mol. Cell 43, 973–981 (2011). [PubMed]