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INTRAFLAGELLAR TRANSPORT

Dynein tails: how to hitch a ride on an IFT train

Nature Structural & Molecular Biology volume 26, pages 760–761 (2019)Cite this article

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Researchers have sought to understand the function and regulation of the motor protein dynein since its discovery more than 50 years ago1. Dynein-2 is one of the motors that move the intraflagellar transport (IFT) trains ― large protein complexes that are needed for the assembly and function of eukaryotic cilia and flagella. Toropova et al. report the single-particle cryo-EM structure of the human dynein-2 complex2, which unexpectedly reveals two different conformations of the motor subunit tails. One tail forms a zigzag that matches the periodicity of the IFT trains, which reinforces the auto-inhibition of dynein motor activity and the binding of multiple dynein-2 complexes along the train during anterograde transport.

Cilia are important for the movement of cells and fluids as well as for the reception and transmission of signals. Genes needed to make cilia constitute at least 5% of the human protein-encoding genes3,4,5, and more than 500 of these proteins are transported into the cilium on IFT trains. Anterograde IFT trains travel from the cytoplasm to the ciliary tip through the use of a kinesin-II motor. Retrograde IFT trains move to the base through the use of the dynein-2 motor complex6. Loss-of-function mutations in the gene encoding dynein heavy-chain 2 cause embryonic lethality in mice. The human syndromes Jeune’s syndrome (asphyxiating thoracic dystrophy (JATD)) and short rib polydactyly syndrome (SRPS) are caused by mutations in dynein-2 and its subunits as well as in other IFT subunits7.

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Fig. 1: The tails of the dynein-2 homodimer subunits show different conformations.

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  1. Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

    Susan K. Dutcher

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Correspondence to Susan K. Dutcher.

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Dutcher, S.K. Dynein tails: how to hitch a ride on an IFT train. Nat Struct Mol Biol 26, 760–761 (2019). https://doi.org/10.1038/s41594-019-0285-z

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