Bionanoscience (BN) seminar by prof. Joshua Shaevitz (Princeton University, USA) on "The mechanism and function of branching microtubule nucleation". Lunch is provided.

This lecture is part of the Hot Topics in Bionanoscience series. For registration and more information, see here.

Abstract: Microtubules are generated at centrosomes, chromosomes, and within spindles during cell division. Whereas microtubule nucleation at the centrosome is well characterized, much remains unknown about where, when, and how microtubules are nucleated at chromosomes. We have recently found that branching microtubule nucleation through the regulation of $\gamma$-TuRC can drive the assembly of acentrosomal spindles. A hydrodynamic instability produces droplets of the wetted protein TPX2 on microtubules which serve as nucleation sites for $\gamma$-TuRC binding and microtubule polymerization. To investigate this process near chromosomes, we reconstituted microtubule nucleation from purified chromosomes in meiotic Xenopus egg extract and found that chromosomes alone can form spindles. We visualized microtubule nucleation at chromosomes to find that this occurs through branching microtubule nucleation. The initial branches nucleate near and towards kinetochores, helping explain how kinetochores might be efficiently captured. By depleting molecular motors, we find that the organization of the resultant polar branched networks is consistent with a theoretical model where the effectors for branching nucleation, such as TPX2, are released by chromosomes, forming a concentration gradient around them that spatially biases branching nucleation. In the presence of motors, these branched networks are organized into multipolar spindles.