Α γ-tubulin complex-dependent pathway suppresses ciliogenesis by promoting cilia disassembly.

The primary cilium, a microtubule-based sensory organelle, undergoes cycles of assembly and disassembly that govern the cell cycle progression critical to cell proliferation and differentiation. Although cilia assembly has been studied extensively, the molecular mechanisms underlying cilia disassembly are less well understood. Here, we uncover a γ-tubulin ring complex (γ-TuRC)-dependent pathway that promotes cilia disassembly and thereby prevents cilia formation. We further demonstrate that Kif2A, a kinesin motor that bears microtubule-depolymerizing activity, is recruited to the cilium basal body in a γ-TuRC-dependent manner. Our mechanistic analyses show that γ-TuRC specifically recruits Kif2A via the GCP2 subunit and its binding partner Mzt2. Hence, despite the long-standing view that γ-TuRC acts mainly as a microtubule template, we illustrate that its functional heterogeneity at the basal body facilitates both microtubule nucleation and Kif2A recruitment-mediated regulation of ciliogenesis, ensuring cell cycle progression.
Competing Interests: Author contributions S.S. and T.-L.H. performed biochemical experiments. S.S., Z.-T.H., A.E., C.-C.L., R.V., and S.-Y.T. carried out cell-based experiments. E.C. and B.R. performed mass spectrometry analysis. S.S. and K.-C.H. determined crystal structures. C.G. performed molecular dynamics simulations. All authors analyzed the data, discussed the results, and helped write the manuscript. J.L., S.-Y.T., and K.-C.H. directed the project. K.-C.H. prepared the manuscript. Declaration of interests The authors declare no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)