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Title page for ETD etd-05222017-140610

Type of Document Dissertation
Author Cadar, Adrian Gabriel
Author's Email Address adrian.gabriel.cadar@gmail.com
URN etd-05222017-140610
Title Titin regulation and maintenance in the cardiac sarcomere
Degree PhD
Department Molecular Physiology and Biophysics
Advisory Committee
Advisor Name Title
Charles E. Cobb, PhD Committee Chair
Anne K. Kenworthy, PhD Committee Member
Charles C. Hong, MD/PhD Committee Member
Chee C. Lim, PhD Committee Member
Owen McGuinness, PhD Committee Member
Wenbiao Chen, PhD Committee Member
  • titin
  • sarcomere
  • FRAP
  • hiPSC
  • hiPSC-CMs
Date of Defense 2017-05-15
Availability restricted
The giant myofilament protein titin is indispensable for the structural integrity and function of the sarcomere, however, little is known regarding the turnover of titin within the complex macromolecular sarcomere structure in contracting cardiomyocytes. This dissertation presents novel and unique insight into the homeostatic control of titin in the cardiac sarcomere; nevertheless, the projects described in this dissertation served to elucidate key components in our understanding of the titin life cycle. The experiments described in the following chapters have addressed 3 major findings. 1) Titin is post-transcriptionally regulated at its 5’-UTR via cis-regulatory uORFs. 2) Titin is post-transcriptionally regulated by miR-26a/b at its 3’-UTR. 3) Titin is not a dynamic and mobile protein that is undergoing continuous exchange between myofibrils.
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