Type of Document	Thesis
Author	Compton, Lisa Ann
Author's Email Address	lisaanncompton@hotmail.com
URN	etd-04092006-223927
Title	Cardiac Thin Filament Regulatory Proteins – Familial Hypertrophic Cardiomyopathy Mutations and Post-Translational Modifications
Degree	Master of Science
Department	Biological Science, Department of
Advisory Committee	Advisor Name Title B. Bryant Chase Committee Member J. Michael Overton Committee Member Peter G. Fajer Committee Member Thomas C. S. Keller III Committee Member Timothy S. Moerland Committee Member
Keywords	In Vitro Motility Heart Tropomyosin Troponin
Date of Defense	2006-01-27
Availability	unrestricted
Abstract The cardiac thin filament is a highly ordered regulatory system for cardiac contraction. Regulatory proteins, a-tropomyosin (a-Tm) and troponin (cTn, composed of cTnT, cTnI, and cTnC), provide a Ca2+-dependent mechanism for controlling actin-myosin interactions that underlie cardiac muscle contraction and relaxation. These regulatory proteins may be altered or modified in a variety of ways in vivo, e.g. by mutation or post-translational modifications, which can alter the function and possibly the structure of the whole heart over time scales both short (beat-to-beat) and long (years). Familial Hypertrophic Cardiomyopathy (FHC) is a disease caused by genetic mutations in sarcomeric genes, notably cTnI and a-Tm, that result in left and/or right ventricular hypertrophy. Three cTnI FHC mutations (P82S, D196N, and S199N) are characterized in Chapter 1 in relation to the modulation of their respective Ca2+-sensitivities of individual actin filaments in the in vitro motility assay. One a-Tm FHC mutant (E180G) that causes an increase in Ca2+-sensitivity in the in vitro motility assay is further studied in Chapter 2. Chapter 3 characterizes a commercially available cTn sample from Research Diagnostics for post-translational modifications.
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