Familial cardiomyopathies occur due to inherited mutations in various genes in the heart. When a gene is mutated, the protein made from the mutated gene will also be faulty. One such gene is CSRP3, which makes the protein Muscle LIM Protein (MLP). MLP is an important protein for the heart’s function. When the heart is stressed, MLP transduces signals so that the heart muscle cells can alter their function to adapt to the stressor. For MLP to transduce stress signals, it likely must bind to proteins with a stress-sensing ability.
In our recent study, we investigated the interaction between MLP and the stress-sensing protein syndecan-4. We found that these proteins interact with one another in the nucleus of heart muscle cells, an important site for cellular responses to be initiated. Some of the inherited mutations in MLP which are known to cause heart disease, disrupted the binding to syndecan-4.
The breakup of these proteins may make the heart muscle cells unable to properly respond to stress, and as such, disease develops. Mutations in MLP also decreased MLP self-association and altered where in the heart muscle cells MLP localized, which are likely modes by which mutations in MLP cause disease. Understanding the microscopic dance between proteins like these in the heart, and how mutations cause them to break up, is an important step toward understanding the intricate mechanisms leading to heart disease.
