REGULATION OF RENAL PHOSPHATE TRANSPORT BY LIPIDS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This work focuses on the effect of liquid ordered membrane domains on renal phosphate transport and regulation. Phosphate transport is dominated by the sodium phosphate cotransporter, NaPi-2a, in the proximal tubule brush border membrane (BBM). Under conditions of severely reduced phosphate intake, the expression of NaPi-2a is up regulated and the BBM NaPi-2a concentration increases significantly. Nevertheless, this does not result in a commensurate increase in phosphate transport activity. Studies on GUVs constructed from rat BBM fractions of the proximal tubule suggest that the samples from the rats with reduced phosphate intake exhibit lower translational mobility and increased clustering of the NaPi-2a transporter.Ultracentrifugation studies showed that the NaPi-2a was preferentially partitioned into cholesterol-, sphingomyelin- and glycosphingolipid- enriched fractions. Future studies will attempt to characterize the link between lipid raft association and reduced NaPi-2a activity .