Biochemical Modification and Subcellular Trafficking of Urea Transporters

Urea and urea transporters (UT) are critical to the production of concentrated urine and hence in maintaining body fluid balance. The UT-A1 urea transporter is the major and most important UT isoform in the kidney. Native UT-A1, expressed in the terminal inner medullary collecting duct (IMCD) epithelial cells, is a glycosylated protein with two glycoforms of 117 and 97 kDa. Vasopressin is the major hormone in vivo that rapidly increases urea permeability in the IMCD through increasing the phosphorylation and apical plasma membrane accumulation of UT-A1. The cell signaling pathway for vasopressin-mediated UT-A1 phosphorylation and activity involves two cAMP-dependent signaling pathways: protein kinase A (PKA) and exchange protein activated by cAMP (Epac). UT-A3 is the NH₂-terminal half of UT-A1, exhibiting similarities and dissimilarities with UT-A1. In this chapter, we will discuss UT-A1 and UT-A3 regulation by phosphorylation, ubiquitination and glycosylation.