Dataset Information

Resolving titin's lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes.

ABSTRACT: Cardiac protein homeostasis, sarcomere assembly, and integration of titin as the sarcomeric backbone are tightly regulated to facilitate adaptation and repair. Very little is known on how the >3-MDa titin protein is synthesized, moved, inserted into sarcomeres, detached, and degraded. Here, we generated a bifluorescently labeled knockin mouse to simultaneously visualize both ends of the molecule and follow titin's life cycle in vivo. We find titin mRNA, protein synthesis and degradation compartmentalized toward the Z-disk in adult, but not embryonic cardiomyocytes. Originating at the Z-disk, titin contributes to a soluble protein pool (>15% of total titin) before it is integrated into the sarcomere lattice. Titin integration, disintegration, and reintegration are stochastic and do not proceed sequentially from Z-disk to M-band, as suggested previously. Exchange between soluble and integrated titin depends on titin protein composition and differs between individual cardiomyocytes. Thus, titin dynamics facilitate embryonic vs. adult sarcomere remodeling with implications for cardiac development and disease.

SUBMITTER: Rudolph F

PROVIDER: S-EPMC6911189 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Resolving titin's lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes.

Rudolph Franziska F Hüttemeister Judith J da Silva Lopes Katharina K Jüttner René R Yu Lily L Bergmann Nora N Friedrich Dhana D Preibisch Stephan S Wagner Eva E Lehnart Stephan E SE Gregorio Carol C CC Gotthardt Michael M

Proceedings of the National Academy of Sciences of the United States of America 20191122 50

Cardiac protein homeostasis, sarcomere assembly, and integration of titin as the sarcomeric backbone are tightly regulated to facilitate adaptation and repair. Very little is known on how the >3-MDa titin protein is synthesized, moved, inserted into sarcomeres, detached, and degraded. Here, we generated a bifluorescently labeled knockin mouse to simultaneously visualize both ends of the molecule and follow titin's life cycle in vivo. We find titin mRNA, protein synthesis and degradation compartm ...[more]

PMID: 31757849

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Dataset Information

Resolving titin's lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes.

Publications

Resolving titin's lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes.

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