In situ architecture of the ciliary base reveals the stepwise assembly of IFT trains
he transition zone, then as it extends into the cytosol, first the dynein-1b and then the IFTA densities are missing. This suggests the IFTB backbone is built first, followed by IFTA and then dynein-2 recruitment. Kinesin-2 is relatively small and flexible and so could not be identified by cryo-ET. Instead, the authors use expansion microscopy to show that this is the final component recruited.
The transition zone and assembling IFT trains. Left: cryo-ET image taken from preprint figure 1. Right: Representative tomogram taken from preprint figure 2: yellow = IFTB; orange = IFTA; red = dynein1b; purple = stellate fibers; turquoise = Y-links; dark blue = MTD helical sleeve; grey = microtubules (added schematic).
I chose this preprint because it beautifully visualises the mysterious early stages of IFT train assembly. The events occurring at the basal body prior to cilium entry are essential in regulating cilium behaviour, both when it comes to building its structure and in determining its signalling capabilities, yet we know so little about them. Elucidating the mechanism of IFT train assembly helps shed light on how IFT is regulated to balance trafficking and ensure that only functional trains can take up valuable space on the axonemal highway. It is also a key step towards unravelling how the transition zone can function as a selective gate. The importance of all of these processes is evidenced by the devastating consequences of mutations in genes encoding IFT and transition zone proteins, which lead to a set of pleiotropic diseases termed ‘ciliopathies’.