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The major facilitator superfamily (MFS) transporter  Pho84  and the type III transporter  Pho89  are responsible for metabolic effects of inorganic phosphate in yeast. While the  Pho89  ortholog  Pit1  was also shown to be involved in phosphate-activated MAPK in mammalian cells, it is currently unknown, whether orthologs of  Pho84  have a role in phosphate-sensing in metazoan species. We show here that the activation of MAPK by phosphate observed in mammals is conserved in  Drosophila  cells, and used this assay to characterize the roles of putative phosphate transporters. Surprisingly, while we found that RNAi-mediated knockdown of the fly  Pho89  ortholog  dPit  had little effect on the activation of MAPK in  Drosophila  S2R+ cells by phosphate, two  Pho84 /SLC17A1–9 MFS orthologs (MFS10 and MFS13) specifically inhibited this response. Further, using a  Xenopus  oocyte assay, we show that MSF13 mediates uptake of [ 33 P]-orthophosphate in a sodium-dependent fashion. Consistent with a role in phosphate physiology, MSF13 is expressed highest in the  Drosophila  crop, midgut, Malpighian tubule, and hindgut. Altogether, our findings provide the first evidence that  Pho84  orthologs mediate cellular effects of phosphate in metazoan cells. Finally, while phosphate is essential for  Drosophila  larval development, loss of MFS13 activity is compatible with viability indicating redundancy at the levels of the transporters.

Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila