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The intraflagellar transport cycle

Nature Reviews Molecular Cell Biology volume 26, pages 175–192 (2025)Cite this article

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Abstract

Primary and motile cilia are eukaryotic organelles that perform crucial roles in cellular signalling and motility. Intraflagellar transport (IFT) contributes to the formation of the highly specialized ciliary proteome by active and selective transport of soluble and membrane proteins into and out of cilia. IFT is performed by the IFT-A and IFT-B protein complexes, which together link cargoes to the microtubule motors kinesin and dynein. In this Review, we discuss recent structural and mechanistic insights on how the IFT complexes are first recruited to the base of the cilium, how they polymerize into an anterograde IFT train, and how this complex imports cargoes from the cytoplasm. We will describe insights into how kinesin-driven anterograde trains are carried to the ciliary tip, where they are remodelled into dynein-driven retrograde trains for cargo export. We will also present how the interplay between IFT-A and IFT-B complexes, motor proteins and cargo adaptors is regulated for bidirectional ciliary transport.

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Fig. 1: Schematic cartoons of motile and primary cilia.
Fig. 2: Components of the intraflagellar transport (IFT) system.
Fig. 3: Overview of the IFT cycle.

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Acknowledgements

This work is supported by the Human Technopole and the European Research Council under the EU Horizon 2020 Research and Innovation Programme (grant number 819826) to G.P.

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  1. Human Technopole, Milan, Italy

    Samuel E. Lacey & Gaia Pigino

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  1. Samuel E. Lacey
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  2. Gaia Pigino
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S.E.L. researched data for the article. Both authors contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Gaia Pigino.

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Nature Reviews Molecular Cell Biology thanks Saikat Mukhopadhyay, who co-reviewed with Venkata Vivek Reddy Palicharla, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Ciliopathies

A group of syndromes with diverse developmental phenotypes caused by mutations to genes involved in the formation and function of cilia.

Cryo-electron tomography

An electron microscopy technique capable of visualizing cellular ultrastructure in three dimensions.

Ectosomes

Small vesicles released from the tip of the cilium that can contain high concentrations of receptors and signalling proteins.

Expansion microscopy

A super-resolution fluorescence microscopy technique in which a sample is cross-linked to an expandable hydrogel to physically separate the resolvable features.

G-protein-coupled receptors

(GPCRs). Integral membrane proteins that transduce the binding of an extracellular agonist into an intracellular response through activation of cytoplasm G proteins.

Polycystic kidney disease

A set of ciliopathy diseases characterized by the aberrant formation of cysts in the kidneys.

Steady-state cilium

A full-length cilium that is neither growing or shrinking.

Tetratricopeptide repeats

A short structural motif made up of antiparallel α-helices that is generally repeated in tandem to form a TPR domain; these often form solenoids or long helical bundles that mediate protein–protein interactions and allow for structural flexibility.

Tryptophan–aspartic acid (WD) domains

β-propeller (annular) structural domains that often mediate protein–protein interactions.

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Lacey, S.E., Pigino, G. The intraflagellar transport cycle. Nat Rev Mol Cell Biol 26, 175–192 (2025). https://doi.org/10.1038/s41580-024-00797-x

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