Figure 1. Truncated titin is present in the myocardial sarcomere and transmits force from the Z-disk to the thick filament.

(A) Schematic showing titin frameshift truncation and the associated C-terminal FS-Ag against which a specific FS-Ab has been made. (B) Western blot showing that the FS-Ab detects truncated titin and not full-length titin. NF, nonfailing. (C) Human cryo-crushed cardiomyocyte fragments from patient 1371 and a control heart labeled with truncated titin FS-Ab in green and anti–Z-disk titin in blue. (D) Quantification and images of fragments from patient 1371 stained as above and stretched. (E) Cardiomyocyte fragments from patient 1371, labeled as above, that were stretched, imaged, treated with 400 mM KCl, and re-imaged. Quantifications are from 47 or more sarcomeres per state, ± SEM. (F) Schematic showing that truncated titin bears load across the sarcomere and is attached to both the Z-disk and thick filament.