| First Author | Weinert S | Year | 2006 |
| Journal | J Cell Biol | Volume | 173 |
| Issue | 4 | Pages | 559-70 |
| PubMed ID | 16702235 | Mgi Jnum | J:111284 |
| Mgi Id | MGI:3653555 | Doi | 10.1083/jcb.200601014 |
| Citation | Weinert S, et al. (2006) M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere. J Cell Biol 173(4):559-70 |
| abstractText | Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains. Titin's M-line region contains a unique kinase domain that has been proposed to regulate sarcomere assembly via its substrate titin cap (T-cap). In this study, we use a titin M line-deficient mouse to show that the initial assembly of the sarcomere does not depend on titin's M-line region or the phosphorylation of T-cap by the titin kinase. Rather, titin's M-line region is required to form a continuous titin filament and to provide mechanical stability of the embryonic sarcomere. Even without titin integrating into the M band, sarcomeres show proper spacing and alignment of Z discs and M bands but fail to grow laterally and ultimately disassemble. The comparison of disassembly in the developing and mature knockout sarcomere suggests diverse functions for titin's M line in embryonic development and the adult heart that not only involve the differential expression of titin isoforms but also of titin-binding proteins. |
