Abstract:
:Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrate that phosphodiesterase type 3A (PDE3A) physically and functionally interacts with cystic fibrosis transmembrane conductance regulator (CFTR) channel. PDE3A inhibition generates compartmentalized cyclic adenosine 3',5'-monophosphate (cAMP), which further clusters PDE3A and CFTR into microdomains at the plasma membrane and potentiates CFTR channel function. Actin skeleton disruption reduces PDE3A-CFTR interaction and segregates PDE3A from its interacting partners, thus compromising the integrity of the CFTR-PDE3A-containing macromolecular complex. Consequently, compartmentalized cAMP signaling is lost. PDE3A inhibition no longer activates CFTR channel function in a compartmentalized manner. The physiological relevance of PDE3A-CFTR interaction was investigated using pig trachea submucosal gland secretion model. Our data show that PDE3A inhibition augments CFTR-dependent submucosal gland secretion and actin skeleton disruption decreases secretion.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Penmatsa H,Zhang W,Yarlagadda S,Li C,Conoley VG,Yue J,Bahouth SW,Buddington RK,Zhang G,Nelson DJ,Sonecha MD,Manganiello V,Wine JJ,Naren APdoi
10.1091/mbc.e09-08-0655subject
Has Abstractpub_date
2010-03-15 00:00:00pages
1097-110issue
6eissn
1059-1524issn
1939-4586pii
E09-08-0655journal_volume
21pub_type
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