| First Author | Musa H | Year | 2006 |
| Journal | J Cell Sci | Volume | 119 |
| Issue | Pt 20 | Pages | 4322-31 |
| PubMed ID | 17038546 | Mgi Jnum | J:116079 |
| Mgi Id | MGI:3692827 | Doi | 10.1242/jcs.03198 |
| Citation | Musa H, et al. (2006) Targeted homozygous deletion of M-band titin in cardiomyocytes prevents sarcomere formation. J Cell Sci 119(Pt 20):4322-31 |
| abstractText | Titin, a multifunctional protein that stretches from the Z-disk to the M-band in heart and skeletal muscle, contains a kinase domain, phosphorylation sites and multiple binding sites for structural and signalling proteins in the M-band. To determine whether this region is crucial for normal sarcomere development, we created mouse embryonic stem cell (ES) lines in which either one or both alleles contained a targeted deletion of the entire M-band-coding region, leaving Z-disk-binding and myosin-filament-binding sites intact. ES cells were differentiated into cardiomyocytes, and myofibrillogenesis investigated by immunofluorescence microscopy. Surprisingly, deletion of one allele did not markedly affect differentiation into cardiomyocytes, suggesting that a single intact copy of the titin gene is sufficient for normal myofibrillogenesis. By contrast, deletion of both alleles resulted in a failure of differentiation beyond an early stage of myofibrillogenesis. Sarcomeric myosin remained in non-striated structures, Z-disk proteins, such as alpha-actinin, were mainly found in primitive dot-like structures on actin stress fibres, M-band-associated proteins (myomesin, obscurin, Nbr1, p62 and MURF2) remained punctate. These results show that integration of the M-band region of titin is required for myosin filament assembly, M-band formation and maturation of the Z-disk. |
