Sul1 and Sul2 sulfate transceptors signal to protein kinase A upon exit of sulfur starvation.

The Journal of Biological Chemistry
Harish Nag KankipatiJohan M Thevelein

Abstract

Sulfate is an essential nutrient with pronounced regulatory effects on cellular metabolism and proliferation. Little is known, however, about how sulfate is sensed by cells. Sul1 and Sul2 are sulfate transporters in the yeast Saccharomyces cerevisiae, strongly induced upon sulfur starvation and endocytosed upon the addition of sulfate. We reveal Sul1,2-dependent activation of PKA targets upon sulfate-induced exit from growth arrest after sulfur starvation. We provide two major arguments in favor of Sul1 and Sul2 acting as transceptors for signaling to PKA. First, the sulfate analogue, d-glucosamine 2-sulfate, acted as a non-transported agonist of signaling by Sul1 and Sul2. Second, mutagenesis to Gln of putative H(+)-binding residues, Glu-427 in Sul1 or Glu-443 in Sul2, abolished transport without affecting signaling. Hence, Sul1,2 can function as pure sulfate sensors. Sul1(E427Q) and Sul2(E443Q) are also deficient in sulfate-induced endocytosis, which can therefore be uncoupled from signaling. Overall, our data suggest that transceptors can undergo independent conformational changes, each responsible for triggering different downstream processes. The Sul1 and Sul2 transceptors are the first identified plasma membrane sensors f...Continue Reading

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Citations

Jun 20, 2019·Open Biology·Emmanuel Mikros, George Diallinas
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Methods Mentioned

BETA
PCR
immunoprecipitation
confocal microscopy
oligoubiquitination

Software Mentioned

ASW
PHOBIUS
Bioinformatics Toolkit
FV10
ClustalX

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