The Zinc Sensing Receptor, ZnR/GPR39, in Health and Disease

Abstract

A distinct G-protein coupled receptor that senses changes in extracellular Zn²⁺, ZnR/GPR39, was found in cells from tissues in which Zn²⁺ plays a physiological role. Most prominently, ZnR/GPR39 activity was described in prostate cancer, skin keratinocytes, and colon epithelial cells, where zinc is essential for cell growth, wound closure, and barrier formation. ZnR/GPR39 activity was also described in neurons that are postsynaptic to vesicular Zn²⁺ release. Activation of ZnR/GPR39 triggers Gαq-dependent signaling and subsequent cellular pathways associated with cell growth and survival. Furthermore, ZnR/GPR39 was shown to regulate the activity of ion transport mechanisms that are essential for the physiological function of epithelial and neuronal cells. Thus, ZnR/GPR39 provides a unique target for therapeutically modifying the actions of zinc in a specific and selective manner.

Keywords: ZnR/GPR39; bone; colon; epithelium; intestine; keratinocyte; neuron; zinc; zinc signaling.

Figure 1

Schematic representations of common Zn²⁺ sensing receptor, ZnR/GPR39, signaling in epithelial cells. Extracellular signal–regulated kinases, ERK; Phosphatidylinositol-4,5-bisphosphate 3 (PI3) kinase/AKT, PI3K/AKT; Phospholipase C, PLC.