Ligand-binding domain of the membrane guanylyl cyclase C
Ligand-binding domain of the membrane guanylyl cyclase C (GC-C or StaR). StaR is a key receptor for the STa (Escherichia coli Heat Stable enterotoxin), a potent stimulant of intestinal chloride and bicarbonate secretion that cause acute secretory diarrhea. The catalytic domain of the STa/guanylin receptor type membrane GC is highly similar to those of the natriuretic peptide receptor (NPR) type and sensory organ-specific type membrane GCs (GC-D, GC-E and GC-F). The GC-C receptor is mainly expressed in the intestine of most vertebrates, but is also found in the kidney and other organs. Moreover, GC-C is activated by guanylin and uroguanylin, endogenous peptide ligands synthesized in the intestine and kidney. Consequently, the receptor activation results in increased cGMP levels and phosphorylation of the CFTR chloride channel and secretion.