Physical and Functional Coupling of CFTR and PDE3A

<p>Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrated that phosphodiesterase type 3A (PDE3A) is physically and functionally coupled to cystic fibrosis transmembrane conductance regulator (CFTR). PDE3A inhibition increases cyclic adenosine 3′, 5′-monophosphate (cAMP) levels in a compartmentalized manner at the plasma membrane, which potentiates CFTR channel function and further clusters PDE3A and CFTR into microdomains. Actin skeleton disruption reduces PDE3A-CFTR interaction; segregates PDE3A from its interacting partners thus compromise the integrity of the macromolecular complex. Consequently, PDE3A inhibition no longer activates CFTR channel function in a compartmentalized manner. Physiologically, formation of the CFTR-PDE3A-containing macromolecular complexes was investigated using pig trachea submucosal gland secretion model. PDE3A inhibition augments CFTR-dependent submucosal gland secretion and actin skeleton disruption decreases secretion. These findings are important in understanding the regulation of CFTR function by phosphodiesterases.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2009

Author dc:creator

• Penmatsa, Himabindu

Contributors dc:contributor

• Anjaparavanda P. Naren, Ph.D.

• cAMP signaling
• CFTR
• FRET
• PDE3A
• single particle tracking
• submucosal secretion
• Cells
• Medicine and Health Sciences

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/204

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1201