Roles of major facilitator superfamily transporters in phosphate response in Drosophila.
Roles of major facilitator superfamily transporters in phosphate response in Drosophila.
复制标题
DOI：
10.1371/journal.pone.0031730
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Perrimon N
中科院分区：
文献类型：
--
作者：
Bergwitz C;Rasmussen MD;DeRobertis C;Wee MJ;Sinha S;Chen HH;Huang J;Perrimon N
主要易化超家族（MFS）转运蛋白Pho 84和III型转运蛋白Pho 89负责无机磷酸盐在酵母中的代谢效应。虽然Pho 89的直系同源物Pit 1也被证明参与哺乳动物细胞中磷酸盐激活的MAPK，但目前尚不清楚Pho 84的直系同源物是否在后生动物物种中的磷酸盐敏感中发挥作用。在这里，我们发现，在哺乳动物中观察到的磷酸活化MAPK在果蝇细胞中是保守的，并使用这种测定来表征假定的磷酸转运蛋白的作用。令人惊讶的是，虽然我们发现RNAi介导的果蝇Pho 89直系同源物dPit的敲除对磷酸盐激活果蝇S2 R+细胞中的MAPK几乎没有影响，但两个Pho 84/SLC 17 A1 -9 MFS直系同源物（MFS 10和MFS 13）特异性地抑制了这种反应。此外，使用非洲爪蟾卵母细胞测定，我们表明，MSF 13介导的摄取[33 P]-正磷酸钠依赖的方式。与磷酸盐生理学中的作用一致，MSF 13在果蝇作物、中肠、马氏管和后肠中表达最高。总之，我们的研究结果提供了第一个证据表明，Pho 84直系同源物介导的磷酸盐在后生动物细胞的细胞效应。最后，虽然磷酸盐是果蝇幼虫发育所必需的，但MFS 13活性的丧失与活力相容，表明转运蛋白水平上的冗余。
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.
登录
查看更多内容
DOI：
10.1056/nejmoa0706130
发表时间：
2008-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gutiérrez OM;Mannstadt M;Isakova T;Rauh-Hain JA;Tamez H;Shah A;Smith K;Lee H;Thadhani R;Jüppner H;Wolf M
通讯作者：
Wolf M
影响因子：
6.2
作者：
Julien, Marion;Khoshniat, Solmaz;Guicheux, Jerome
通讯作者：
Guicheux, Jerome
DOI：
10.1159/000223693
发表时间：
2009-01-01
期刊：
CALCIUM AND BONE DISORDERS IN CHILDREN AND ADOLESCENTS
影响因子：
--
作者：
Bergwitz, Clemens;Jueppner, Harald
通讯作者：
Jueppner, Harald
DOI：
10.1165/rcmb.2005-0477oc
发表时间：
2006-11-01
影响因子：
6.4
作者：
Chang, Seung-Hee;Yu, Kyeong Nam;Cho, Myung-Haing
通讯作者：
Cho, Myung-Haing
影响因子：
48
作者：
Kulkarni, Meghana M.;Booker, Matthew;Mathey-Prevot, Bernard
通讯作者：
Mathey-Prevot, Bernard