Structure, Interactions, and Dynamic Self-assembly of Tau and Tubulin

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. Tau proteins that stabilize MT, are major determinants of cytoskeleton stability. Malfunctions of tubulin and tau are involved in various pathologies including cancer and neurodegenerative diseases. We propose to reconstitute in vitro minimal model systems that mimic these key elements of the cytoskeleton, and follow, in real-time, their coassembled dynamic structures, stability, and interactions. Using SAXS and time-resolved SAXS we will determine the structures and intermolecular forces dictating the various ways tubulin dimers dynamically nucleate, assemble, and interact with one another to stabilize and form MT.