Beyond translation: the renal phosphate census. Focus on 'Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule'

摘要

the addition of a single phosphate group to a protein can cause dramatic and varied changes in its function: it can change an ion channel's open probability (31), trigger the activation of an entire signaling cascade (17), or cause a protein to translocate to the cell surface (30). Phosphorylation is a particularly efficient way to regulate cell signaling, in that the effect is rapid and the modification can be quickly reversed, allowing for dynamic regulation. Indeed, phosphorylation is the most evolutionarily conserved posttranslational modification and is key for proper function of cells found in the kidney. The renal cortex of the kidney comprises a variety of epithelial cells [including proximal tubule, thick ascending limb, distal convoluted tubule (DCT), and cortical collecting duct cells], all of which have a primary transport function (Fig. 1). In addition, the renal cortex contains the podocytes and mesangial cells of the glomeralus. While the proximal tubule and thick ascending limb mainly function in reabsorption, the more distal nephron segments (the DCT, connecting tubule, and collecting duct) have important roles in reabsorption and secretion. By volume, the vast majority of the cells in the cortex are proximal tubule cells. Proximal tubules have highly developed dense apical brash border membranes, which aid in reabsorbing two-thirds of the glomerular filtrate, while the more distal segments have a much smaller surface-to-volume ratio.