Physiological Reviews, Vol. 80, No. 4, October 2000, pp. 1373-1409
Copyright ©2000 by the American Physiological Society

Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms

Institute of Physiology, University of Zürich, Zürich, Switzerland

Murer, Heini, Nati Hernando, Ian Forster, and Jürg Biber. Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms. Physiol. Rev. 80: 1373-1409, 2000.Renal proximal tubular reabsorption of P_i is a key element in overall P_i homeostasis, and it involves a secondary active P_i transport mechanism. Among the molecularly identified sodium-phosphate (Na/P_i) cotransport systems a brush-border membrane type IIa Na-P_i cotransporter is the key player in proximal tubular P_i reabsorption. Physiological and pathophysiological alterations in renal P_i reabsorption are related to altered brush-border membrane expression/content of the type IIa Na-P_i cotransporter. 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-P_i cotransporter, the cellular cascades involved in "physiological/pathophysiological" control of P_i 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-P_i cotransporter (in 1993) provided the tools to study renal brush-border membrane Na-P_i 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 P_i handling and, thus, of overall P_i homeostasis.