On Day 3 of the 2013 EMBO meeting in Amsterdam, I attended a great afternoon session on cytoskeletal dynamics.
Carolyn Moores kicked things off by describing how her lab uses cryo-electron microscopy to determine the structures of microtubules and their associated regulatory factors. You might wonder how examining the static structures of microtubules tells you anything about their dynamics. But identifying how microtubule-associated proteins bind to microtubules reveals a great deal about their function. In a 2010 JCB paper, for example, Moores and colleagues showed that the microtubule-stabilizing protein doublecortin binds at the intersection of four tubulin heterodimers, revealing how the protein can stabilize both lateral and longitudinal contacts between the microtubule subunits. And, in 2012, Moores and colleagues showed how microtubule plus-end tracking proteins (+TIPs) of the EB family bind close to the tubulin GTPase site, suggesting how the proteins might be able to sense the nucleotide-binding state of tubulin subunits at the growing ends of microtubules.
Many additional +TIPs bind to EB proteins at the plus ends of microtubules through a core motif containing the amino acid sequence SxIP. Anna Akhmanova described her lab’s recent proteomic screen to identify new +TIPs that contain this motif. According to Akhmanova, almost every cellular structure that interacts with microtubules has its own +TIP.
Simone Reber (from Tony Hyman’s laboratory) described how the microtubule polymerase XMAP-215 regulates the size of the mitotic spindle. The spindle’s length scales with the level of XMAP-215 activity; as XMAP-215’s activity is reduced, the spindle shrinks in size. Interestingly, echoing Hyman’s Saturday evening talk on the importance of phase transitions in cell biology, Reber’s model of spindle regulation treats the spindle as an active liquid crystal.
The session’s chairperson, Marileen Dogterom, discussed her lab’s approach to studying cytoskeletal dynamics, in which they attempt to reconstitute microtubule behavior in minimal, in vitro systems. They’ve successfully used this approach to study how cortical dynein positions microtubule asters, and her group is currently looking at how microtubules cooperate with the actin cytoskeleton.
By Dogterom’s own admission, actin was a little underrepresented in the talks, but Omaya Dudin (a member of Sophie Martin’s group in Lausanne) rounded the session off nicely with a beautiful study of how the actin cytoskeleton promotes the fusion of mating fission yeast cells.