NITROGEN LIMITATION ADAPTATION Recruits PHOSPHATE2 to Target the Phosphate Transporter PT2 for Degradation during the Regulation of Arabidopsis Phosphate Homeostasis

Phosphate homeostasis is tightly modulated in all organisms, including bacteria, which harbor both high- and low-affinity transporters acting under conditions of fluctuating phosphate levels. It was thought that nitrogen-fixing rhizobia, named bacteroids, inhabiting root nodules of legumes are not phosphate limited. Here, we show that the high-affinity phosphate transporter PstSCAB, rather than the low-affinity phosphate transporter Pit, is essential for effective nitrogen fixation of Sinorhizobium fredii in soybean nodules. Symbiotic and growth defects of the pst mutant can be effectively restored by knocking out PhoB, the transcriptional repressor of pit. The pst homologs of representative rhizobia were actively transcribed in bacteroids without terminal differentiation in nodules of diverse legumes (soybean, pigeonpea, cowpea, common bean, and Sophora flavescens) but exhibited a basal expression level in terminally differentiated bacteroids (alfalfa, pea, and peanut). Rhizobium leguminosarum bv. viciae Rlv3841 undergoes characteristic nonterminal and terminal differentiations in nodules of S. flavescens and pea, respectively. The pst mutant of Rlv3841 showed impaired adaptation to the nodule environment of S. flavescens but was indistinguishable from the wild-type strain in pea nodules. Taken together, root nodule rhizobia can be either phosphate limited or nonlimited regarding the rhizobial differentiation fate, which is a host-dependent feature.

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Faculty Opinions recommendation of PROTEIN PHOSPHATASE95 regulates phosphate homeostasis by affecting phosphate transporter trafficking in rice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737190486.793573401 ◽

2020 ◽

Author(s):

Jian Feng Ma

Keyword(s):

Phosphate Transporter ◽

Phosphate Homeostasis

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Vacuolar Phosphate Transporter 1 (VPT1) Affects Arsenate Tolerance by Regulating Phosphate Homeostasis in Arabidopsis

Plant and Cell Physiology ◽

10.1093/pcp/pcy025 ◽

2018 ◽

Cited By ~ 6

Author(s):

Mingda Luan ◽

Jinlong Liu ◽

Yuewen Liu ◽

Xingbao Han ◽

Guangfang Sun ◽

...

Keyword(s):

Phosphate Transporter ◽

Phosphate Homeostasis ◽

Arsenate Tolerance

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Distinct domains within the NITROGEN LIMITATION ADAPTATION protein mediate its subcellular localization and function in the nitrate-dependent phosphate homeostasis pathway

Botany ◽

10.1139/cjb-2017-0149 ◽

2018 ◽

Vol 96 (2) ◽

pp. 79-96 ◽

Cited By ~ 1

Author(s):

Carol Hannam ◽

Satinder K. Gidda ◽

Sabrina Humbert ◽

Mingsheng Peng ◽

Yuhai Cui ◽

...

Keyword(s):

Plasma Membrane ◽

Nitrogen Limitation ◽

Mutational Analysis ◽

Phosphate Homeostasis ◽

Phosphate Transporters ◽

Starvation Response ◽

Protein Motifs ◽

Phosphate Starvation Response ◽

And Function ◽

Linker Domain

The NITROGEN LIMITATION ADAPTATION (NLA) protein is a RING-type E3 ubiquitin ligase that plays an essential role in the regulation of nitrogen and phosphate homeostasis. NLA is localized to two different subcellular sites (the plasma membrane and the nucleus), and contains four distinct domains: (i) a RING domain that mediates degradation of phosphate transporters at the plasma membrane; (ii) an SPX domain that facilitates NLA’s interaction with the phosphate transporters, and also exists in other proteins that regulate the nuclear transcription factors that control the phosphate starvation response pathway; (iii) a linker domain that lies between the RING and SPX domains; and (iv) a C-terminal domain, which, like the linker region, is of unknown function. Here we carried out a mutational analysis of NLA, which indicated that all the domains are not only essential for proper functioning of the protein, but also mediate its localization to the plasma membrane and (or) nucleus, as well as to different subdomains within the nucleus. Overall, the results provide new insights to the distinct protein motifs within NLA and the role(s) that this protein serves at different subcellular sites with respect to the regulation of nitrogen-dependent phosphate homeostasis as well as other possible physiological functions.

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PROTEIN PHOSPHATASE95 Regulates Phosphate Homeostasis by Affecting Phosphate Transporter Trafficking in Rice

The Plant Cell ◽

10.1105/tpc.19.00685 ◽

2020 ◽

Vol 32 (3) ◽

pp. 740-757 ◽

Cited By ~ 4

Author(s):

Zhili Yang ◽

Jian Yang ◽

Yan Wang ◽

Fei Wang ◽

Wenxuan Mao ◽

...

Keyword(s):

Phosphate Transporter ◽

Phosphate Homeostasis

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MO053INHIBITION OF SODIUM PHOSPHATE TRANSPORTER NPT2A IMPROVES EXPERIMENTAL VASCULAR CALCIFICATION AND PHOSPHATE HOMEOSTASIS IN RATS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa140.mo053 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Juergen Klar ◽

Giese Anja ◽

Alexander Ehrmann ◽

Christoph Thiel ◽

Bernd Riedl ◽

...

Keyword(s):

Vascular Calcification ◽

Plasma Levels ◽

Calcium Content ◽

Treated Group ◽

Phosphate Transporter ◽

Phosphate Homeostasis ◽

Simultaneous Treatment ◽

Phosphate Excretion ◽

Male Wistar Rats ◽

Fgf 23

Abstract Background and Aims A dysregulated phosphate homeostasis is strongly associated with mortality, cardiovascular events and vascular calcification, particularly in patients suffering from CKD. Inhibition of the tubular phosphate transporter Npt2a provides a novel and unique mechanism to address phosphate homeostasis imbalance and vascular calcification. Method Npt2a activity was measured in a cell-based assay, using a stable CHO cell line with inducible Npt2a expression. Male Wistar rats were used for all experiments. Healthy rats were treated orally with BAY 767, a potent Npt2a inhibitor developed at Bayer AG to assess urinary phosphate excretion. Vascular calcification was induced by administration of a pan-FGFR inh. (25mg/kg) for 10 days. Calcium content in the aorta was measured as surrogate for vascular calcification. Blood samples were withdrawn at the end of the study to determine the plasma levels of FGF-23, parathyroid hormone and phosphate with commercially available assay systems according to the manufactures protocols (FGF-23 and PTH: ELISA Kit, Immuntopics; phosphate: Pentra400 system). Results BAY 767 was identified as potent Npt2a inhibitor, with an IC50 of 2.9/6 nM on rat/ human Npt2a, respectively, selective over Npt2b, Npt2c and Pit-1. Single dose treatments of healthy rats resulted in a significant, dose-dependent increase in urinary phosphate excretion within 16h. In an experimental vascular calcification model, massive vascular calcification and hyperphosphatemia was induced by daily oral administration of a FGFR inh. Simultaneous treatment with the Npt2a inhibitor BAY 767 significantly inhibited vascular calcification in comparison to untreated rats. In this set-up the plasma phosphate level was increased after 10 days up to 3.7 mmol/L in the FGFR inh. treated group compared to 1.9 mmol/L in control animals, whilst treatment with BAY 767 reduced plasma levels to 2.7 mmol/L. In addition, FGF-23 and PTH were also reduced under compound BAY 767 treatment. However, in the same model 2.2% lanthanum carbonate was not beneficial with respect to vascular calcification. Conclusion Our results show for the first time that treatment with a Npt2a inhibitor improves vascular calcification by addressing urinary phosphate excretion and phosphate homeostasis in rats. Npt2a inhibition may provide a new therapeutic principle for patients suffering from disbalanced phosphate homeostasis and vascular calcifications, including CKD patients.

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