Year: 2022
Type: article
Abstract: 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.
Source: Cell
Authors: Sophie J. Hesketh, Aakash G. Mukhopadhyay, Dai Nakamura, Katerina Toropova, Anthony J. Roberts
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $9,900
Awards: Cryo electron microscope for high-resolution single particle analysis, G339059223, Cryo electron microscope for high-resolution single particle analysis, Dynein-2: Building and maintaining a functional primary cilium, State of the art cryo electron microscope for molecular and cellular biology, State of the art cryo electron microscope for molecular and cellular biology, G9000046662
OpenAlex ID: W4310668128