Discovery of a novel link between cilia and material properties of microtubules
Guha, Mayukh Mukul
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Microtubules are hollow cylindrical polymers of α and β tubulin heterodimers. Being the most rigid component of the cellular cytoskeleton, microtubules are associated with several mechanical functions. They bear the compressive load generated by motor proteins and actomyosin contractility. They withstand forces during transport of large cargoes like the nucleus, chromosomes and mitochondria. Their stiffness helps in the contraction of cardiac muscles. Such deforming forces often lead to buckling and breaking of cytoplasmic microtubules. Microtubules are the major structural elements of cellular projections called cilia. They enable the cilia to perform a perpetual rhythmic motion that generates enough force to propel cells and move extracellular fluid. The precise waveform and mechanical properties of the cilium are mainly attributed to microtubules. Despite producing such high forces, structural deformations have not been reported in the microtubules of wild-type cilia. Using a unicellular ciliated organism Tetrahymena thermophila, we attribute the mechanical stability of some ciliary microtubules to a conserved ciliary protein, SPEF1 – a protein related to microtubule end binding (EB) proteins. We show that a pair of microtubules critical for normal ciliary motility, the central pair, is susceptible to mechanical forces and that SPEF1 protects them from mechanical damage. In the absence of SPEF1, the central microtubules acquire gaps consistent with internal breakages. The structural defects of central microtubules in the SPEF1-null cilia are aggravated by artificial mechanical force and partially rescued by chemical inhibition of ciliary motility. By showing that SPEF1 protects the central microtubules from mechanical damage, we have discovered the ciliary function of SPEF1. We also found that microtubules, like most non-biological materials, could be more sensitive to tensile stress as compared to compressive stress. Interestingly, while SPEF1 evidently co-evolved with the central pair microtubules, it could potentially play a stabilizing role on several sub-types of non-ciliary microtubules.