Structure and dynamics of the cilium transport system by cryo-ET et al.

In this talk I will show how we combine EM and molecular cell biology methods to obtain a mechanistic understanding of the molecular machineries required for the assembly and the function of cilia/flagella: evolutionary conserved organelles with fundamental roles in human health and disease. Assembly of the cilium requires the rapid bidirectional transport (intraflagellar transport or IFT) of building blocks to and from the site of assembly at its tip. IFT trains is driven by the anterograde motor kinesin-2 and the retrograde motor dynein-1b, which are both bound to two large protein complexes made of about 25 IFT adaptors. We developed methods, from time resolve CLEM to in vitro reconstitution of IFT motility on synthetic microtubules, through mechanical manipulation of cells, to investigate the dynamics and regulation of IFT trains. With cryo-ET and AlphaFold2 we solved the structure of entire anterograde and …