Fig. 4.

Mammalian cells possess 2 adenylyl cyclase (AC) systems. Transmembrane adenylyl cyclases are anchored into the plasma membrane and when stimulated by forskolin or G_αs generate cAMP in the subplasma membrane compartment. Phosphodiesterases (PDE), critically located at the periphery of the compartment, hydrolyze cAMP to 5′-AMP. In contrast, mammalian soluble adenylyl cyclase 10 (sAC) lacks transmembrane domains and localizes to the centrosome, microtubules, nucleus, and mitochondria. When stimulated by bicarbonate and calcium, sAC generates a phosphodiesterase sensitive cAMP pool in the cytosolic compartment (adapted from Ref. 182).