Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation
ABSTRACT The fission yeast PHO regulon genes pho1, pho84, and tgp1—encoding a cell surface-associated acid phosphatase (Pho1), a plasma membrane inorganic phosphate transporter (Pho84), and a plasma membrane glycerophosphocholine transporter (Tgp1)—are strongly upregulated in response to acute phosp...
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American Society for Microbiology
2025-01-01
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02992-24 |
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| author | Aleksei Innokentev Ana M. Sanchez Mara Monetti Beate Schwer Stewart Shuman |
| author_facet | Aleksei Innokentev Ana M. Sanchez Mara Monetti Beate Schwer Stewart Shuman |
| author_sort | Aleksei Innokentev |
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| description | ABSTRACT The fission yeast PHO regulon genes pho1, pho84, and tgp1—encoding a cell surface-associated acid phosphatase (Pho1), a plasma membrane inorganic phosphate transporter (Pho84), and a plasma membrane glycerophosphocholine transporter (Tgp1)—are strongly upregulated in response to acute phosphate starvation, as are the SPBPB2B2.06c and SPAC1039.02 genes that encode putative 5'-nucleotidase paralogs of the binuclear metallophosphoesterase enzyme superfamily. Via proteomic analysis of the medium harvested from phosphate-replete and phosphate-starved fission yeast, we define a starvation secretome that includes SPBPB2B2.06c (renamed Efn1, for extracellular five-prime nucleotidase), SPAC1039.02 (henceforth Efn2), and Pho1 among the most abundant exported proteins elaborated by phosphate-starved cells. We demonstrate and characterize a 5'-nucleotidase activity secreted into the medium of phosphate-starved efn1+efn2+ cells, which is eliminated by simultaneous deletion of efn1 and efn2. By singly deleting efn1 and efn2, we find that Efn1 contributes the greater share of secreted 5'-nucleotidase activity. Efn1 and Efn2 catalyze the release of inorganic phosphate from all four standard ribonucleoside monophosphates, in order of preference: CMP > UMP > AMP > GMP. Whereas efn1+efn2+ cells can use extracellular CMP as a source of phosphate during phosphate starvation, efn1∆ efn2∆ cells cannot. The secretion of 5'-nucleotidase enzymes during phosphate limitation is a newly appreciated facet of fission yeast phosphate homeostasis.IMPORTANCESchizosaccharomyces pombe 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. |
| format | Article |
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| institution | Kabale University |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Society for Microbiology |
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| spelling | doaj-art-85cb2fec99de405eb38a93d2c77ff0442025-01-08T14:00:38ZengAmerican Society for MicrobiologymBio2150-75112025-01-0116110.1128/mbio.02992-24Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvationAleksei Innokentev0Ana M. Sanchez1Mara Monetti2Beate Schwer3Stewart Shuman4Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USAMolecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USAProteomics Core Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York, USADepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USAMolecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USAABSTRACT The fission yeast PHO regulon genes pho1, pho84, and tgp1—encoding a cell surface-associated acid phosphatase (Pho1), a plasma membrane inorganic phosphate transporter (Pho84), and a plasma membrane glycerophosphocholine transporter (Tgp1)—are strongly upregulated in response to acute phosphate starvation, as are the SPBPB2B2.06c and SPAC1039.02 genes that encode putative 5'-nucleotidase paralogs of the binuclear metallophosphoesterase enzyme superfamily. Via proteomic analysis of the medium harvested from phosphate-replete and phosphate-starved fission yeast, we define a starvation secretome that includes SPBPB2B2.06c (renamed Efn1, for extracellular five-prime nucleotidase), SPAC1039.02 (henceforth Efn2), and Pho1 among the most abundant exported proteins elaborated by phosphate-starved cells. We demonstrate and characterize a 5'-nucleotidase activity secreted into the medium of phosphate-starved efn1+efn2+ cells, which is eliminated by simultaneous deletion of efn1 and efn2. By singly deleting efn1 and efn2, we find that Efn1 contributes the greater share of secreted 5'-nucleotidase activity. Efn1 and Efn2 catalyze the release of inorganic phosphate from all four standard ribonucleoside monophosphates, in order of preference: CMP > UMP > AMP > GMP. Whereas efn1+efn2+ cells can use extracellular CMP as a source of phosphate during phosphate starvation, efn1∆ efn2∆ cells cannot. The secretion of 5'-nucleotidase enzymes during phosphate limitation is a newly appreciated facet of fission yeast phosphate homeostasis.IMPORTANCESchizosaccharomyces pombe 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.https://journals.asm.org/doi/10.1128/mbio.02992-24Schizosaccharomyces pombephosphate starvationphosphate scavenging5'-nucleotidase |
| spellingShingle | Aleksei Innokentev Ana M. Sanchez Mara Monetti Beate Schwer Stewart Shuman Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation mBio Schizosaccharomyces pombe phosphate starvation phosphate scavenging 5'-nucleotidase |
| title | Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation |
| title_full | Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation |
| title_fullStr | Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation |
| title_full_unstemmed | Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation |
| title_short | Efn1 and Efn2 are extracellular 5'-nucleotidases induced during the fission yeast response to phosphate starvation |
| title_sort | efn1 and efn2 are extracellular 5 nucleotidases induced during the fission yeast response to phosphate starvation |
| topic | Schizosaccharomyces pombe phosphate starvation phosphate scavenging 5'-nucleotidase |
| url | https://journals.asm.org/doi/10.1128/mbio.02992-24 |
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