Compartmentalized cyclic adenosine 3′,5′-monophosphate at the plasma membrane clusters PDE3A and cystic fibrosis transmembrane conductance regulator into microdomains

Himabindu Penmatsa, Weiqiang Zhang, Sunitha Yarlagadda, Chunying Li, Veronica G. Conoley, Junming Yue, Suleiman Bahouth, Randal Buddington, Guangping Zhang, Deborah J. Nelson, Monal D. Sonecha, Vincent Manganiello, Jeffrey J. Wine, Anjaparavanda P. Naren

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1097-1110
Number of pages14
JournalMolecular Biology of the Cell
Volume21
Issue number6
DOIs
StatePublished - Mar 15 2010

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Type 3 Cyclic Nucleotide Phosphodiesterases
Cystic Fibrosis Transmembrane Conductance Regulator
Adenosine
Cell Membrane
Skeleton
Actins
Macromolecular Substances
Multiprotein Complexes
Trachea
Swine

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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Compartmentalized cyclic adenosine 3′,5′-monophosphate at the plasma membrane clusters PDE3A and cystic fibrosis transmembrane conductance regulator into microdomains. / Penmatsa, Himabindu; Zhang, Weiqiang; Yarlagadda, Sunitha; Li, Chunying; Conoley, Veronica G.; Yue, Junming; Bahouth, Suleiman; Buddington, Randal; Zhang, Guangping; Nelson, Deborah J.; Sonecha, Monal D.; Manganiello, Vincent; Wine, Jeffrey J.; Naren, Anjaparavanda P.

In: Molecular Biology of the Cell, Vol. 21, No. 6, 15.03.2010, p. 1097-1110.

Research output: Contribution to journalArticle

Penmatsa, Himabindu ; Zhang, Weiqiang ; Yarlagadda, Sunitha ; Li, Chunying ; Conoley, Veronica G. ; Yue, Junming ; Bahouth, Suleiman ; Buddington, Randal ; Zhang, Guangping ; Nelson, Deborah J. ; Sonecha, Monal D. ; Manganiello, Vincent ; Wine, Jeffrey J. ; Naren, Anjaparavanda P. / Compartmentalized cyclic adenosine 3′,5′-monophosphate at the plasma membrane clusters PDE3A and cystic fibrosis transmembrane conductance regulator into microdomains. In: Molecular Biology of the Cell. 2010 ; Vol. 21, No. 6. pp. 1097-1110.
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AU - Nelson, Deborah J.

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