(Pro)renin Receptor in Kidney Development and Disease

Figure 3

Proposed mechanisms mediating the effect of the (pro)renin receptor (PRR) in metanephric kidney development. (a): PRR interacts with Wnt receptor frizzled (Fz) to regulate polarization and intercalation of collecting duct (CD) cells via planar cell polarity (PCP)/convergent extension (CE) Wnt signaling pathway [16, 25, 79]. (b): PRR may regulate UB branching by (1) inhibiting c-kit transcription via promyelocytic zinc finger transcription factor (PLZF) [73, 83, 84] (2) induction of Erk1/2, PI3K/Akt or epidermal growth factor receptor (EGFR) phosphorylation [52, 72, 73, 75, 85–87], and (3) interaction with LRP5/6 Wnt coreceptor leading to activation of β-catenin and Ret gene expression [22, 23, 56]. (c): PRR interacts with LRP5/6 and V-ATPase to form a complex at the plasma membrane. Following endocytosis, V-ATPase generates a gradient of H⁺ ions that is essential for LRP5/6 phosphorylation and activation of β-catenin [56]. V-ATPase stimulates Notch signaling [88]. Notch acts to define the podocyte and proximal tubular cell fates [89] and regulates differentiation of the CD cells [90].