Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation

<i>Schizosaccharomyces pombe</i> adapts to phosphate starvation by upregulating the expression of a cell surface acid phosphatase that mobilizes inorganic phosphate from the extracellular milieu, as well as transmembrane transporters that take up inorganic phosphate and glycerophosphocholine. This study identifies two paralogous extracellular 5'-nucleotidase enzymes, Efn1 and Efn2, encoded by genes that are highly transcriptionally induced during acute phosphate starvation, as major proteins secreted into the medium by phosphate-starved fission yeast cells. Secreted Efn1 and Efn2 catalyze the release of inorganic phosphate from all ribonucleoside monophosphates, with a preference for CMP. Secretion of Efn1 and Efn2 enables phosphate-starved fission yeast to thrive by using extracellular CMP as a source of inorganic phosphate. The starvation-induced production of extracellular 5'-nucleotidases adds a new layer of pro-adaptive function during phosphate limitation.