This application is founded on data showing that expression of connexin45 in cells containing connexin43 alters gap junction communication in those cells. The data suggest that Cx43 and Cx45 interact to form gap junction with unique properties.
Three specific aims are proposed. First, the investigator will characterize the interaction between Cx43 and Cx45. Second, he will determine the molecular basis for such interaction mainly through a series of site-directed mutagenesis studies. Third, he will establish the possible significance of these interactions on chemical and electrical coupling.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054660-03
Application #
6180846
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Shapiro, Bert I
Project Start
1998-05-01
Project End
2002-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
3
Fiscal Year
2000
Total Cost
$216,703
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Laing, James G; Saffitz, Jeffrey E; Steinberg, Thomas H et al. (2007) Diminished zonula occludens-1 expression in the failing human heart. Cardiovasc Pathol 16:159-64
Laing, J G; Koval, M; Steinberg, T H (2005) Association with ZO-1 correlates with plasma membrane partitioning in truncated connexin45 mutants. J Membr Biol 207:45-53
Laing, James G; Chou, Brian C; Steinberg, Thomas H (2005) ZO-1 alters the plasma membrane localization and function of Cx43 in osteoblastic cells. J Cell Sci 118:2167-76
Lin, George C; Rurangirwa, Jacqueline K; Koval, Michael et al. (2004) Gap junctional communication modulates agonist-induced calcium oscillations in transfected HeLa cells. J Cell Sci 117:881-7
Jorgensen, Niklas R; Henriksen, Zanne; Sorensen, Ole H et al. (2002) Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors. J Biol Chem 277:7574-80
Laing, J G; Manley-Markowski, R N; Koval, M et al. (2001) Connexin45 interacts with zonula occludens-1 and connexin43 in osteoblastic cells. J Biol Chem 276:23051-5
Jorgensen, N R; Henriksen, Z; Brot, C et al. (2000) Human osteoblastic cells propagate intercellular calcium signals by two different mechanisms. J Bone Miner Res 15:1024-32