New perspectives on secretion of (pro)renin receptor into extracellular space.

(Pro)renin receptor is a new molecule of the renin-angiotensin system. The (pro)renin receptor binds both renin and prorenin leading to protease activity. Furthermore, the binding of renin/prorenin to (pro)renin receptor activates intracellular signaling. Although these studies show the classical function of the (pro)renin receptor on the plasma membrane as a receptor, subcellular distribution and extracellular secretion of (pro)renin receptor remained controversial until recently when Cousin et al. reported possible existence of the soluble form of (pro)renin receptor. Chinese hamster ovary (CHO) cells transfected with human (pro)renin tagged with Venus showed bands at 74 kDa and 35 kDa without any stimulation in Western blot analysis. Moreover, these cells secreted a 29 kDa form, which was the amino-terminal fragment of the (pro)renin receptor. In immunofluorescent staining, (pro)renin receptor tagged with Venus was mainly stained on the endoplasmic reticulum and in vesicle-like structures, but not on the plasma membrane. These data suggest that the (pro)renin receptor may be cleaved in the intracellular compartments of cells and secreted into the extracellular space.