The cotransporter NaPi-IIa: enzyme-dependent activity regulation

The sodium-coupled phosphate transporter NaPi-IIa is the main cellular carrier accomplishing kidney phosphate reabsorption. It is driven by the electrochemical Na+ gradient across the apical cell membrane which is maintained by Na+ extrusion across the basolateral cell membrane through the Na+/K+ ATPase. Energy starvation is sensed by the AMPK a serine/threonine kinase stimulating several cellular mechanisms increasing energy production and limiting energy consumption. AMPK provides a critical link between energy metabolism and cellular transport. The aging suppressor Klotho a transmembrane protein is a protease and hormone has been shown to exert a profound effect on phosphate metabolism aging and lifespan. Additionally the enzymes SGK1 mTOR Akt/PKB and Nedd4-2 are of critical importance for a wide variety of functions including bone mineralization and energy metabolism. The present book explores the mechanisms of phosphate homeostasis and the role of AMPK Klotho SGK1 mTOR Akt/PKB and Nedd4-2 in the regulation of NaPi-IIa activity.