Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms

Abstract

Renal proximal tubular reabsorption of Pi is a key element in overall Pi homeostasis, and it involves a secondary active Pi transport mechanism. Among the molecularly identified sodium-phosphate (Na/Pi) cotransport systems a brush-border membrane type IIa Na-Pi cotransporter is the key player in proximal tubular Pi reabsorption. Physiological and pathophysiological alterations in renal Pi reabsorption are related to altered brush-border membrane expression/content of the type IIa Na-Picotransporter. Complex membrane retrieval/insertion mechanisms are involved in modulating transporter content in the brush-border membrane. In a tissue culture model (OK cells) expressing intrinsically the type IIa Na-Pi cotransporter, the cellular cascades involved in “physiological/pathophysiological” control of Pi reabsorption have been explored. As this cell model offers a “proximal tubular” environment, it is useful for characterization (in heterologous expression studies) of the cellular/molecular requirements for transport regulation. Finally, the oocyte expression system has permitted a thorough characterization of the transport characteristics and of structure/function relationships. Thus the cloning of the type IIa Na-Pi cotransporter (in 1993) provided the tools to study renal brush-border membrane Na-Pi cotransport function/regulation at the cellular/molecular level as well as at the organ level and led to an understanding of cellular mechanisms involved in control of proximal tubular Pi handling and, thus, of overall Pihomeostasis.