Titin - tracking an allrounder and its functions

Titin is the largest protein in the human body and is located in the sarcomere, the molecular unit of the muscle fibres in the musculoskeletal system and the heart. It creates an elastic link between parts of the sarcomere, which move towards each other as the muscle contracts and return to their original position when the muscle is at rest.

Professor Michael Gotthardt and his working group at the Max Delbrueck Center in Berlin are collaborating with colleagues from the University of Arizona and Washington State University to examine the functions of titin in the context of biomechanics, metabolism and signalling pathways. They hope that their research will reveal more about the causes of heart disease and amyotrophy. The titin molecule is made up of 26,000 parts grouped in functional modules. In order to gain an idea of the functions of the various modules, the Gotthardt laboratory has produced mice whose heart muscles produce titin with altered modules. Either a particular module does not function from the start or its production can be switched off. Through these experiments, the researchers have established that titin has many regulatory functions. For example, if the N2B module is switched off, the mouse develops a smaller heart with less elasticity.

Michael Gotthardt and his group of researchers have produced a strain of N2B-KO mice, the first titin-based animal model for diastolic cardiac insufficiency, which is especially prevalent in women. Molecular mechanisms which lead to cardiac insufficiency can be examined using this model; researchers hope that this will enable them to develop new treatment strategies.