Slow but steady: Molecular mechanisms controlling microtubule growth in centrioles and cilia

Microtubules are cytoskeletal filaments that form dynamic cytoplasmic arrays and stable cores of centrioles and cilia. Microtubule dynamics depend on GTP hydrolysis by tubulin: addition of GTP-tubulin creates a stabilizing cap, whereas cap loss triggers depolymerization. In structures with very slowly growing microtubules, such as centrioles and cilia, long GTP caps cannot form; instead, specialized protein complexes stabilize microtubule plus ends and support their slow elongation. Recent studies showed that although centrioles and cilia use distinct proteins to control their microtubule plus ends, the underlying mechanisms are similar. Both rely on complexes combining microtubule growth inhibitors with polymerases that counteract inhibition, which jointly stabilize the plus ends and drive their gradual extension. Both centriolar and ciliary microtubule tip regulators form assemblies that span inner and outer microtubule surfaces and reduce protofilament peeling. Because many centriole and ciliary tip proteins are mutated in human disorders, including microcephaly and ciliopathies, these findings provide insight into the molecular basis of such diseases.