Discovery of a miniature station

Cilia are small, hair-like organelles that extend from cells and perform many functions, including motility and signaling. The researchers have now revealed that the cilia have a specialized transport hub at their base, where trains and cargo are assembled for transport through the cilia. Since defects in this cilia transport system can lead to, for example, cystic kidneys or blindness, the results published in Science also provide new insights into the molecular bases of various diseases.

Cilia perform many functions for the cell: they help cells swim, move fluids and send messages to each other. Cilia allow us to see, they remove substances from the lungs, move fluids in the brain and allow us to perceive smells and sounds. They are also essential for our development and the proper arrangement of our organs. If their function is disrupted, a wide variety of diseases can result, including heart, kidney and lung disease, blindness or infertility.

Cilia assembly and function rely on large trains of proteins that carry important cargoes to the ciliary tip and base. Even the smallest mutations in individual components can cripple traffic inside the cilia.

The research team led by Prof. Ben Engel from the Biozentrum at the University of Basel with colleagues from the University of Geneva and the Human Technopole research institute in Milan have now succeeded in examining the eyelashes in their natural environment. . Their analysis revealed for the first time the native 3D structure of the ciliary base. Here they discovered a busy transport hub, with trains assembled and loaded in preparation for their journey through the eyelashes.

Loading station for transporting eyelashes

Cilia are firmly anchored to the cell at their base. “Here is the starting station for eyelash transport,” says Hugo van den Hoek, first author of the study. “The trains are assembled here, loaded with goods and placed on the tracks.” There are a total of nine different rails inside the cilia, called microtubules. Each of them consists of two tracks, one for outgoing trains and one for incoming trains. The trains carry proteins such as signaling molecules and building materials to the tips of the eyelashes. At their destination station, the train is unloaded and dismantled.

The team examined in detail the composition of the assembly trains, revealing the order in which the components of the train are assembled at the ciliary base. They also imaged structures at the base that serve as a selective barrier. “This regulates the entry of large trains until they are fully assembled and loaded with the cargo proteins needed to build and maintain the cilia,” explains van den Hoek. “Thanks to fluorescence microscopy, we also know the exact schedule of the trains. The trains leave the departure station in nine seconds, and then the whole process of assembling the train starts again.”

3D organelles

The researchers resolved the structure and composition of the ciliary base using two complementary imaging methods. The research groups of Ben Engel in Basel and Dr. Gaia Pigino in Milan performed cryo-electron tomography, which reveals native cellular structures in exquisite molecular detail. Researchers led by Dr. Virginie Hamel and Prof. Paul Guichard in Geneva added data from expansion microscopy, which made it possible to locate and map many proteins on tomography structures. “This powerful combination of technologies allowed us to reconstruct the first molecular model of the ciliary base and to observe how it regulates the assembly and entry of these large protein trains”, explains Paul Guichard.

“Understanding the transport system and its logistics in detail helps us understand how cilia are constructed and function, which can also provide new ideas for therapies for cilia diseases,” says Ben Engel. As a next step, he and his collaborators would like to examine what happens at the ciliary tip: how this terminal station is structured and how the return transport is organised.

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Material provided by University of Basel. Note: Content may be edited for style and length.

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