Molecular determinants for apical expression and regulatory membrane retrieval of the type IIa Na/Pi cotransporter.

Renal inorganic phosphate (Pi) reabsorption is a key process in Pi homeostasis. Type IIa Na/Pi cotransporters, located at the apical membrane of renal proximal tubular cells, guarantee the vectorial transport of Pi. Renal Pi reabsorption can be modulated by controlling the number of cotransporters expressed at the apical membrane. Indeed, factors that increase Pi reabsorption induce the expression of type IIa cotransporters at the apical membrane, whereas factors that decrease Pi reabsorption lead to their retrieval. Therefore, proper sorting of this type of cotransporters is an essential step in Pi homeostasis. The relevance of polarization has been highlighted by the finding that improper sorting of transporters can cause disease. Here we describe the identification of signals involved in apical expression of newly synthesized type IIa cotransporters and in their hormonal-induced endocytosis.