The cell biology and biochemistry of microtubule nucleation

Brouhard GJ

McGill University.

Microtubules are born and reborn continuously, even during quiescence. These polymers are nucleated from templates, namely γ-tubulin ring complexes (γ-TuRCs) and severed microtubule ends. Interestingly, the rate of microtubule nucleation increases as cells enter mitosis, and all cells nucleate microtubules in distinct regions of their cytoplasms. How are these spatial and temporal profiles for microtubule nucleation established? One hypothesis is based on the observation that the rate of microtubule nucleation is strongly affected by both catastrophe factors and anti-catastrophe factors, suggesting an essential relationship between nucleation and catastrophe. Alternatively, the rate of nucleation may be related to the kinetics of microtubule growth and modulated by microtubule polymerases. We do not understand the relative importance of catastrophes versus kinetics in determining a cell’s nucleation profiles. I will discuss my lab’s recent attempts to address this knowledge gap using a mix of single-molecule biophysics, cell biology, and structural biology.