IFT-A structure reveals carriages for membrane protein transport into cilia

Cell. 2022 Dec 22;185(26):4971-4985.e16. doi: 10.1016/j.cell.2022.11.010. Epub 2022 Dec 2.


Intraflagellar transport (IFT) trains are massive molecular machines that traffic proteins between cilia and the cell body. Each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) and motor proteins, posing a formidable challenge to mechanistic understanding. Here, we reconstituted the complete human IFT-A complex and obtained its structure using cryo-EM. Combined with AlphaFold prediction and genome-editing studies, our results illuminate how IFT-A polymerizes, interacts with IFT-B, and uses an array of β-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-A⋅TULP carriages are essential for cilia localization of diverse membrane proteins, as well as ICK-the key kinase regulating IFT train turnaround. These data establish a structural link between IFT-A's distinct functions, provide a blueprint for IFT-A in the train, and shed light on how IFT evolved from a proto-coatomer ancestor.

Keywords: AlphaFold; COPI; Cilia; Cryo-EM; G-Protein Coupled Receptor; Intraflagellar Transport; Membrane Protein; Microtubule; Motor Protein; TULP3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cilia* / metabolism
  • Dyneins / metabolism
  • Flagella / metabolism
  • Humans
  • Kinesins* / metabolism
  • Membrane Proteins / metabolism
  • Protein Transport


  • Kinesins
  • Dyneins
  • Membrane Proteins