Fig. 7.

Working model illustrating cAMP diffusion barricade. Transmembrane AC6 localizes to caveolin-rich lipid rafts in PMVECs with calcium channel proteins and barrier-enhancing molecules such as filamin A and cell adhesion molecules E-cadherin, N-cadherin, and ALCAM. In contrast, VE-cadherin is in the bulk plasma membrane. A: isoproterenol stimulation of transmembrane AC activity generates cAMP, which is restricted to the subplasma membrane compartment by diffusion barricades and leads to the elevated phosphorylation of filamin A at serine 2152. B: P. aeruginosa uses a type III secretion system to inject ExoY into the cytosolic compartment, where it generates cAMP, leading to phosphorylation of the microtubule associating protein, tau, at serine 214. ExoY-generated cAMP does not traverse the diffusion barricade and is unable to phosphorylate filamin at serine 2152.