Abstract

Cell adhesion molecules (CAMs) can mediate both cell-cell and cell-extracellular matrix (ECM) adhesions, aswelt as govern the most fundamental properties within multicellular organisms, including cell morphology,migration, proliferation, differentiation, tissue morphogenesis, and embryonic development. Recent studieshave now also revealed that mutations in genes encoding CAMs are found and associated with variousdiseases, including cancers, autoimmune diseases as well as cardiomyopathiesThis proposal is to test the central hypothesis that cardiac components of cell-cell (ie. plakoglobin), and/orcell-ECM (ie.PINCH) adhesion complexes play important roles in the etiology of arrhythmogenic rightventricular dysplasia/ cardiomyopathy (ARVD/C) and cardiac function and/or repair. Accordingly, the specificaims are:
Specific Aim 1 : To understand the molecular mechanism by which the human plakoglobin mutation results inNaxos disease, a recessive form of ARVD/C.
Specific Aim 2 : To determine whether the ARVD/C phenotype results from a cell autonomous requirementfor plakoglobin in cardiomyocytes and to understand the role of ICD and cytoplasmic/nuclear plakoglobin inthis disease.
Specific Aim 3 : To study the functional role of PINCH in cardiac development, injury, and repair.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL046345-16
Application #
7331349
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
16
Fiscal Year
2007
Total Cost
$250,000
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Dewan, Sukriti; McCabe, Kimberly J; Regnier, Michael et al. (2016) Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study. J Phys Chem B 120:8264-75
Peter, Angela K; Bradford, William H; Dalton, Nancy D et al. (2016) Increased Echogenicity and Radiodense Foci on Echocardiogram and MicroCT in Murine Myocarditis. PLoS One 11:e0159971
Sheikh, Farah; Lyon, Robert C; Chen, Ju (2015) Functions of myosin light chain-2 (MYL2) in cardiac muscle and disease. Gene 569:14-20
Israeli-Rosenberg, Sharon; Chen, Chao; Li, Ruixia et al. (2015) Caveolin modulates integrin function and mechanical activation in the cardiomyocyte. FASEB J 29:374-84
Stroud, Matthew J; Banerjee, Indroneal; Veevers, Jennifer et al. (2014) Linker of nucleoskeleton and cytoskeleton complex proteins in cardiac structure, function, and disease. Circ Res 114:538-48
Zemljic-Harpf, Alice E; Godoy, Joseph C; Platoshyn, Oleksandr et al. (2014) Vinculin directly binds zonula occludens-1 and is essential for stabilizing connexin-43-containing gap junctions in cardiac myocytes. J Cell Sci 127:1104-16
Lyon, Robert C; Mezzano, Valeria; Wright, Adam T et al. (2014) Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a novel mouse model. Hum Mol Genet 23:1134-50
Pfeiffer, E R; Wright, A T; Edwards, A G et al. (2014) Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing. J Mol Cell Cardiol 76:265-74
Bang, Marie-Louise; Gu, Yusu; Dalton, Nancy D et al. (2014) The muscle ankyrin repeat proteins CARP, Ankrd2, and DARP are not essential for normal cardiac development and function at basal conditions and in response to pressure overload. PLoS One 9:e93638
Israeli-Rosenberg, Sharon; Manso, Ana Maria; Okada, Hideshi et al. (2014) Integrins and integrin-associated proteins in the cardiac myocyte. Circ Res 114:572-586

Showing the most recent 10 out of 144 publications