Structure, interactions, and dynamic self-assembly of tubulin with different tau isoforms

Tubulin nucleation and microtubule (MT) assembly are frequent events in cells. The mechanisms directing these processes are poorly understood, owing to the size of tubulin and its highly dynamic character. The MT-associated tau proteins, including six isoforms, are major determinants of axon cytoskeleton stability and dynamics. Malfunctions of tubulin and tau are involved in various pathologies including cancer and neurodegenerative diseases. We propose to use time-resolved solution small-angle-X-ray scattering (TR-SAXS) methods, and our advanced analysis tools to follow the coassembly dynamics of different tubulin with different tau isoforms. Our aim is to determine the structures and intermolecular interactions dictating how tubulin dimers and different tau isoforms dynamically nucleate, assemble, and interact with one another to form tau-stabilized MT.