Researchers have revealed for the first time the original 3D structure of the ciliary base

Cilia are small hair-like organelles that extend from cells and perform many functions, including movement and signaling. Researchers have now revealed that cilia have a specialized transport hub at their base, where trains and goods are assembled for transport throughout the cilia. Since defects in the cilia transport system can lead to cystic kidneys or blindness, the results were published in Sciences It also offers new insights into the molecular basis of a variety of diseases.

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

Cilia assembly and function depend on large trains of proteins that carry important cargos to the ciliary tip and back to the base. Even the smallest mutations in individual components can paralyze the traffic within the cilia.

The research team led by Professor Ben Engel at the Biozentrum at the University of Basel together with colleagues at the University of Geneva and the Human Technopole Research Institute in Milan has successfully examined cilia in their natural environment. Their analysis revealed the original 3D structure of the ciliary base for the first time. Here, they discover a busy transportation hub, where trains are assembled and loaded in preparation for their journey to the Cistern.

Loading station for transferring cilia

Cilia are firmly attached to the cell at their base. “This is the starting station for cilia transfer,” explains Hugo van den Hoek, first author of the study. “The trains are assembled here, loaded with goods and laid on the rails.” There are a total of nine different rods inside the cilia called microtubules. Each consists of two tracks, one for outgoing trains and one for inbound trains. The trains transport proteins such as signaling molecules and building materials to the tip of the cilia. At their destination station, the train is unloaded and disassembled.

The team examined the composition of the assembly trains in detail, revealing the order in which the train components are grouped together at the ciliary base. They also photographed structures at the base that act as a selective barrier.

This regulates the entry of large trains until they are fully assembled and loaded with cargo proteins necessary for building and maintaining cilia. From fluorescence microscopy, we also know the exact timeline of the trains. The trains leave the starting station within nine seconds, and then the entire train assembly process begins again.”

Hugo van den Hoek, first author of the study

3D Organelles

The researchers solved the structure and composition of the ciliary base with the help of two complementary imaging methods. The research team from Ben Engel in Basel and Dr. Gaia Pigino in Milan has performed cold electron tomography, which reveals original cellular structures in exquisite molecular detail. Researchers headed by Dr Virginie Hamill and Professor Paul Gichard in Geneva added data from expansion microscopy, which allowed localization and mapping of many proteins into tomographic structures. “This powerful combination of techniques has allowed us to reconstruct the first molecular model of the ciliary base and 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 build and function, which may also provide new ideas for treatments for cilia disease,” says Ben Engel. In the next step, he and his collaborators would like to examine what happens at the ciliary tip: how this terminal is organized and how return transport is organized.

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Journal reference:

Van den Hoek, H., and others. (2022) The in situ architecture of the ciliary base reveals the gradual assembly of the IFT trains. Sciences. doi.org/10.1126/science.abm6704.