SUN LAB @ NUS
Ciliary Transport
Cilia are slender, hair-like structures that extend from the surface of cells in many different organisms, including humans. These structures play a critical role in a variety of biological processes, including movement, sensory perception, and the maintenance of cellular and tissue structure. For example, in the respiratory system, cilia lining the airways help to move mucus and debris out of the lungs, while in the reproductive system, cilia help to move eggs through the female reproductive tract. In addition, cilia are involved in the development and maintenance of many organs and tissues, including the brain, kidneys, and eyes. Cilia don't contain protein synthesis machinery. Therefore, it relies on the intraflagellar transport (IFT) systems to transport key macromolecules in and out of the cilia. We combine structure, cell biology, and pharmacology approaches to study the intraflagellar transport process and their implications in human health and diseases.
Introduction animation
Credit: Norman Luo and Meiqin Jiang
Structure of IFT-A complexes and insights into IFT-A train formation
Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. Mutations in IFT subunits lead to numerous ciliopathies involving multiple tissues. We reported cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3, a cargo adaptor. IFT-A adopts a “lariat” shape with interconnected core and peripheral subunits linked by structurally vital zinc-binding domains. TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. We also determine the molecular impacts of disease mutations on complex formation and ciliary transport. Our work reveals IFT-A architecture, sheds light on ciliary transport and IFT train formation, and enables the rationalization of disease mutations in ciliopathies.