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Am J Physiol Renal Physiol (November 23, 2004). doi:10.1152/ajprenal.00097.2004
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Submitted on March 24, 2004
Accepted on November 13, 2004

Internalization of renal type IIc Na/Pi cotransporter in response to a high phosphate diet

Hiroko Segawa1, Setsuko Yamanaka1, Mikiko Ito1, Masashi Kuwahata1, Masayuki Shono2, Tadashi Yamamoto3, and Ken-ichi Miyamoto1*

1 Nutrition Science, Department of Nutrition, School of Medicine, Tokushima University, Tokushima, Japan
2 General Laboratory for Medical Research, School of Medicine, Tokushima University, Tokushima, Japan
3 Department of Structual Pathology, Institute of Nephrology Graduate School of Medical and Dental Sciences Niigata University, Niigata, Japan

* To whom correspondence should be addressed. E-mail: miyamoto{at}nutr.med.tokushima-u.ac.jp.

Dietary phosphate levels regulate the renal brush border type IIa Na/Pi cotransporter. Another Na/Pi cotransporter, type IIc, colocalizes with type IIa Na/Pi cotransporter in the apical membrane of renal proximal tubular cells. The goal of the present study was to determine whether dietary phosphate levels also rapidly regulate the type IIc Na/Pi cotransporter. Type IIa and type IIc transporter protein levels were increased in rats chronically fed a low Pi diet compared to those fed a normal Pi diet. Two hours after beginning a high Pi diet, type IIa transporter levels were decreased, whereas type IIc protein levels remained unchanged. Western blot analysis of brush border membrane (BBM) prepared 4 hours after beginning a high Pi diet showed a significant reduction in type IIc transporter protein levels, and immunohistochemistry showed translocation of the type IIc immunoreactive signal from the entire brush border to subapical membrane. Membrane fractionation studies revealed a decrease in apical membrane type IIc protein without changes in total cortical type IIc protein which is compatible with redistribution of type IIc protein from the apical membrane to the dense membrane fraction. The microtubuledisrupting reagent, colchicine, prevented this reduction in apical type IIc transporter at the apical membrane but had no effect on type IIa transporter levels. These data suggest that the type IIc Na/Pi cotransporter level is rapidly regulated by rapid adaptation to dietary Pi in a microtubuledependent manner. Further, the mechanisms of the internalization of the type IIc transporter are distinct from those of the type IIa transporter.




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