Molecular Mechanisms Underlying the Construction of Ciliary Doublet Microtubules.

Abstract

Motile cilia and flagella are complex microtubule-based organelles essential for cell motility, fluid flow, and sensory functions. At the core of these organelles lie doublet microtubules (DMTs), specialized structures consisting of an A-tubule and a B-tubule that serve as the scaffold for axonemal complexes. Recent advances have uncovered the intricate architecture of DMTs, highlighting inner and outer junction proteins, luminal scaffolds, and interdoublet linkers critical for structural stability and function. Studies in model organisms such as Chlamydomonas, Tetrahymena, and Caenorhabditis elegans have identified conserved regulators orchestrating DMT assembly. Parallel insights from human genetics reveal that mutations in DMT-associated proteins underlie a subset of cases of primary ciliary dyskinesia and other ciliopathies. This review synthesizes current understanding of DMT biogenesis from molecular, structural, and disease perspectives, illuminating how coordinated assembly ensures ciliary function and how its disruption leads to human disease.