8.A.85 The Guanylate Cyclase (GC) Family
cGMP controls many cellular functions ranging from growth, viability, and differentiation to contractility, secretion, and ion transport. The mammalian genome encodes seven transmembrane guanylyl cyclases (GCs), GC-A to GC-G, which mainly modulate submembrane cGMP microdomains (Kuhn 2016). These GCs share a unique topology comprising an extracellular domain, a short transmembrane region, and an intracellular COOH-terminal catalytic (cGMP synthesizing) region. GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides, regulating arterial blood pressure/volume and energy balance. GC-B is activated by C-type natriuretic peptides, stimulating endochondral ossification. GC-C mediates the paracrine effects of guanylins on intestinal ion transport and epithelial turnover. GC-E and GC-F are expressed in photoreceptor cells of the retina, and their activation by intracellular Ca2+-regulated proteins is essential for vision. Finally, in the rodent system two olfactorial GCs, GC-D and GC-G, are activated by low concentrations of CO2 and by peptidergic guanylins and nonpeptidergic odorants as well as by low temperatures, which have implications for social behaviors (Kuhn 2016).