Centriole structure, function, & assembly

Deciphering the molecular architecture of one of the cell's most intricate organelles

Centrioles are evolutionarily conserved, microtubule-based organelles that play essential roles in cell division, centrosome organization, and the formation of cilia and flagella. Despite their remarkably conserved ninefold symmetrical architecture, how hundreds of proteins assemble into a functional centriole, maintain its structural integrity, and support its diverse cellular functions remains incompletely understood. Defects in centriole assembly or function are associated with numerous human diseases, including ciliopathies, microcephaly, infertility, and cancer.

Our laboratory aims to uncover the molecular principles governing centriole architecture, assembly, and function. By combining cryo-electron tomography (cryo-ET), Ultrastructure Expansion Microscopy (U-ExM), quantitative imaging, and functional approaches, we investigate the centriole across molecular, ultrastructural, and cellular scales.

Our work has revealed key structural elements of the centriole, including the inner scaffold and the A–C linker, and has provided a time-resolved molecular framework for understanding human centriole assembly. 

Ultimately, our goal is to understand how the centriole is built, how its architecture supports its functions, and how disruption of this organization contributes to human disease.

Centriole (also called basal body) is amongst the largest macromolecular complex of the human cell

Understanding how the molecular architecture of centrioles supports their diverse cellular functions requires knowing where individual proteins are located, how they are spatially organized, and how this organization evolves during centriole assembly. By precisely mapping the localization of centriolar proteins, we aim to uncover the molecular principles governing the formation and organization of this highly structured organelle. Combining this spatial information with the timing of protein recruitment, we have reconstructed the successive stages of human centriole assembly, from the earliest naked cartwheel through procentriole formation and elongation to the fully mature centriole. This time-resolved molecular reconstruction provides a framework for understanding how the intricate architecture of centrioles is progressively established and how their structural organization underpins their cellular functions.

Click on the video below to see the centriole assembly process ⬇

Model of the human centriole assembly - see Laporte et al. Cell. 2024 - 10.1016/j.cell.2024.03.025

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