This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long-term goal of our laboratory is to understand the mechanisms by which information is encoded within second messenger signals, including Ca2+ and cAMP. These signaling pathways are known to regulate diverse processes including cellular excitability, proliferation, and gene expression. Our understanding of Ca2+ signals has increased dramatically over the last 30 years, primarily due to the development of single-cell methods for measuring intracellular Ca2+. Our understanding of cAMP signals, however, has lagged behind, largely due to the lack of high-resolution, single-cell measurement techniques. Only recently have reliable approaches for measuring cAMP signals in single cells been developed. These approaches have provided an unprecedented view of cyclic nucleotide signals near the plasma membranes of several cell types. We have used these approaches to provide evidence suggesting that the effective diffusion coefficient of cAMP is considerably slower than had been previously thought (~10,000-fold slower movement than by free diffusion alone). In addition, elegant studies demonstrated that compartmentalized cAMP signals are critical for barrier function in pulmonary microvascular endothelial cells (PMVECs). Based upon these studies, we propose testing the following working hypothesis: phosphodiesterase activity, buffering, and anomalously slow cAMP diffusion localize cAMP signals in pulmonary microvascular endothelial cells.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR013186-14
Application #
8362509
Study Section
Special Emphasis Panel (ZRG1-CB-L (40))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
14
Fiscal Year
2011
Total Cost
$10,544
Indirect Cost
Name
University of Connecticut
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
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