Physiological Relevance of Renin/Prorenin Binding and Uptake

There is compelling physiological evidence of binding and uptake of renin and prorenin in tissues. A number of molecules with the ability to bind renin and prorenin have been identified and have been characterized to varying degrees. It remains unclear, however, just how many renin/prorenin binding proteins and receptors exist and what their physiological functions may be. The possible functions of renin/prorenin binding and uptake are manifold, and include clearance of renin and prorenin from the circulation, local generation of angiotensins, activation of prorenin on the cell surface, trafficking of prorenin between cellular and extracellular compartments as part of a complex processing machinery, and signal transduction both via direct receptor mediated signaling, and via modulation of O-linkage of N-acetyl-glucosamine to cellular proteins. Some of these functions may involve single renin/prorenin binding sites or receptors, while others may require multiple binding sites and receptors. This review describes the physiological studies that have provided evidence of renin/prorenin uptake from the circulation, summarizes our knowledge of renin/prorenin binding proteins and receptors, and postulates new roles for renin/prorenin binding and uptake in tissues.