Autosomal dominant polycystic kidney disease (ADPKD) affects millions of people and it is the fourth leading cause of kidney failure in the United States. The two genes encoded in this disease are PKD1 and PKD2, and mutations in either gene are associated with the phoenotype seen in ADPKD. The long-term objective entails PKD2 gene product, polycystin-2, functions as a calcium permeable nonselective cation channel. Dysregulation of this channel provides mechanism for the onset and progression of ADPKD.
The specific aims of this research include to (1) Determine the interaction between polycystin-2 and the ryanodine receptor (RYR); (2) What effects mutated variants of polycystin-2 would impact on the function of polycystin-2; (3) Develop a screening assay for putative agonists and antagonists of PKD2. Since these channels are intracellular calcium channels, planar lipid bilayer and calcium imaging techniques will be used to perform this study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DK062635-02
Application #
6834594
Study Section
Special Emphasis Panel (ZRG1-F10 (29))
Program Officer
Agodoa, Lawrence Y
Project Start
2003-09-01
Project End
2006-08-31
Budget Start
2004-08-31
Budget End
2005-08-30
Support Year
2
Fiscal Year
2004
Total Cost
$25,172
Indirect Cost
Name
Yale University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Anyatonwu, Georgia I; Estrada, Manuel; Tian, Xin et al. (2007) Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2. Proc Natl Acad Sci U S A 104:6454-9
Anyatonwu, Georgia I; Ehrlich, Barbara E (2005) Organic cation permeation through the channel formed by polycystin-2. J Biol Chem 280:29488-93