Roles of Major Facilitator Superfamily Transporters in Phosphate Response in \(Drosophila\)
Rasmussen, Matthew D.
Wee, Mark J.
Chen, Hway H.
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CitationBergwitz, Clemens, Matthew D. Rasmussen, Charles DeRobertis, Mark J. Wee, Sumi Sinha, Hway H. Chen, Joanne Huang, and Norbert Perrimon. 2012. Roles of major facilitator superfamily transporters in phosphate response in \(Drosophila\). PLoS ONE 7(2): e31730.
AbstractThe major facilitator superfamily (MFS) transporter \(Pho84\) and the type III transporter \(Pho84\) are responsible for metabolic effects of inorganic phosphate in yeast. While the \(Pho84\) 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 \(Pho84\) 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 [33P]-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.
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