The tubulin code as mechanism for context-dependent fine-tuning of microtubule functions – TUBTUNE

The microtubule cytoskeleton is an evolutionarily conserved macromolecular assembly with a large variety of functions in living cells. Adaptation to specific functions is likely controlled by the tubulin code, a molecular mechanism to diversify microtubules. Here we will develop a systems approach to determine the molecular mechanisms and biological role of the posttranslational modification polyglutamylation, which due to its complexity and dynamic nature generates many combinatory patterns on microtubules. We aim at demonstrating how specific polyglutamylation patterns determine the functions of microtubules in neurons in a locally and temporally controlled manner. To reach this goal, we will develop superresolution-microscopy based tools to visualize different polyglutamylation patterns in cells, identify their physiological roles in neurons, and use proteomics and in vitro reconstitution experiments to decipher by which molecular mechanisms polyglutamylation controls its biological functions.