Without titin's kinase domain, the heart initially develops properly (left), but degenerates under strain (right).
The giant protein called titin is a major component of muscles. Its COOH terminus, also known as the M-line region, includes a kinase-like domain. In yeast two-hybrid assays, titin's M-line interacts with proteins that shuttle to and from the nucleus, leading scientists to believe that it might initiate sarcomere assembly via signaling pathways.
A mouse strain lacking the kinase-like domain and nearby regions, however, reveals that the domain is not necessary for sarcomere assembly. These mice died during embryogenesis, but histological images revealed that sarcomere assembly and heart formation were initially normal. The lethal defect was heart failure due to a lack of sarcomere thickening—the addition of more...
