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First published online December 20, 2007

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Phosphodiesterase cAMPs it up

Within blood vessels, endothelial cells form a tightly regulated barrier to prevent extrusion of fluid through the vessel wall. Barrier integrity requires the uneven intracellular distribution of cAMP, which is concentrated close to the plasma membrane – where it is generated – and more dilute elsewhere. This biphasic distribution is maintained by phosphodiesterase (PDE) activity close to the plasma membrane, which metabolises cAMP to block its diffusion into the bulk cytosol. Now Troy Stevens and colleagues (p. 110) show that PDE4D4, a splice variant of a PDE4 isoform, is the enzyme responsible for this activity in pulmonary microvascular endothelial cells. The authors show that PDE4D4 coimmunoprecipitates with spectrin, and that the two proteins colocalise near cell-cell borders, which is consistent with attachment of PDE4D4 to the plasma-membrane-associated cytoskeleton. Expression of a catalytically inactive mutant of PDE4D4 leads to increased cAMP signalling and to weakening of the endothelial cell barrier. These data indicate that PDE4D4 plays a key role in maintaining endothelial barrier integrity.

Related articles in JCS:

Spectrin-anchored phosphodiesterase 4D4 restricts cAMP from disrupting microtubules and inducing endothelial cell gap formation

Judy Creighton, Bing Zhu, Mikhail Alexeyev, and Troy Stevens
JCS 2008 121: 110-119. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content