Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila

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, whe...

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Main Authors: Bergwitz, Clemens, Rasmussen, Matthew D., DeRobertis, Charles, Wee, Mark J., Sinha, Sumi, Chen, Hway H., Huang, Joanne, Perrimon, Norbert
Other Authors: Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Format: Article
Language:en_US
Published: Public Library of Science 2012
Online Access:http://hdl.handle.net/1721.1/70083
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author Bergwitz, Clemens
Rasmussen, Matthew D.
DeRobertis, Charles
Wee, Mark J.
Sinha, Sumi
Chen, Hway H.
Huang, Joanne
Perrimon, Norbert
author2 Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
author_facet Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Bergwitz, Clemens
Rasmussen, Matthew D.
DeRobertis, Charles
Wee, Mark J.
Sinha, Sumi
Chen, Hway H.
Huang, Joanne
Perrimon, Norbert
author_sort Bergwitz, Clemens
collection MIT
description 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 [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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spelling mit-1721.1/700832022-09-27T18:08:46Z Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila Bergwitz, Clemens Rasmussen, Matthew D. DeRobertis, Charles Wee, Mark J. Sinha, Sumi Chen, Hway H. Huang, Joanne Perrimon, Norbert Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Rasmussen, Matthew D. Rasmussen, Matthew D. 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 [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. National Institutes of Health (U.S.) (NIDDK 5K08DK078361) Harvard Catalyst 2012-04-20T16:41:04Z 2012-04-20T16:41:04Z 2012-02 2011-12 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/70083 Bergwitz, Clemens et al. “Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila.” Ed. Shree Ram Singh. PLoS ONE 7.2 (2012): e31730. Web. 20 Apr. 2012. en_US http://dx.doi.org/10.1371/journal.pone.0031730 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS
spellingShingle Bergwitz, Clemens
Rasmussen, Matthew D.
DeRobertis, Charles
Wee, Mark J.
Sinha, Sumi
Chen, Hway H.
Huang, Joanne
Perrimon, Norbert
Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila
title Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila
title_full Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila
title_fullStr Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila
title_full_unstemmed Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila
title_short Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila
title_sort roles of major facilitator superfamily transporters in phosphate response in drosophila
url http://hdl.handle.net/1721.1/70083
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