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1 University of Zaragoza
2 University of Zurich
3 University of Colorado Denver
* To whom correspondence should be addressed. E-mail: IForster{at}access.uzh.ch.
The principal mediators of renal phosphate (Pi) reabsorption are the SLC34 family proteins NaPi-IIa and NaPi-IIc, localized to the proximal tubule (PT) apical membrane. Their abundance is regulated by circulatory factors and dietary Pi. Although their physiological importance has been confirmed in knockout animal studies, significant Pi reabsorptive capacity remains, which suggests the involvement of other secondary-active Pi transporters along the nephron. Here we show that a member of the SLC20 gene family (PiT-2) is localized to the brush border membrane (BBM) of the proximal tubule epithelia and that its abundance, confirmed by Western blot and immunohistochemistry of rat kidney slices, is regulated by dietary Pi. In rats treated chronically on a high-Pi (1.2 %) diet, there was a marked decrease in the apparent abundance of PiT-2 protein in kidney slices compared with those from rats kept a chronic low-Pi (0.1 %) diet. In Western blots of BBM from rats that were switched from a chronic low to high-Pi diet, NaPi-IIa showed rapid down-regulation after 2 hrs, PiT-2 was also significantly down-regulated at 24 hrs, and NaPi-IIc after 48 hrs. For the converse dietary regime, NaPi-IIa showed adaptation within 8 hrs, whereas PiT-2 and NaPi-IIc showed a slower adaptive trend. Our findings suggest that PiT-2, until now considered as a ubiquitously expressed Pi housekeeping transporter, is a novel mediator of Pi reabsorption in the proximal tubule under conditions of acute Pi deprivation, but with a different adaptive time course from NaPi-IIa and NaPi-IIc.
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