REGULATION OF RENAL PHOSPHATE TRANSPORT BY LIPIDS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本文主要研究了液体有序膜结构域对肾脏磷酸盐转运和调节的影响。在近端小管刷状缘膜(BBM)中，磷酸二氢钠共转运体Napi-2a主导着磷酸盐的转运。在磷摄入量严重减少的情况下，napi-2a的表达上调，BBM napi-2a浓度显著增加。然而，这并不会导致磷酸盐转运活动的相应增加。对大鼠近端小管BBM组分构建的GUV的研究表明，磷酸盐摄入量减少的大鼠样本表现出较低的翻译迁移率和较高的Napi-2a转运体聚集性。超速离心法研究表明，Napi-2a优先分配为富含胆固醇、鞘磷脂和鞘糖脂的组份。未来的研究将试图确定脂筏关联和Napi-2a活性降低之间的联系。

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 .