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Microtubule stabilization drives 3D centrosome migration to initiate primary ciliogenesis
Amandine Pitaval1,2, Fabrice Senger2, Gaëlle Letort2
1UMR_S 1038, Biomics Lab, University Grenoble-Alpes, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut National de la Santé et de la Recherche, Institut de Biosciences et Biotechnologies de Grenoble, Grenoble, France.
Abstract:
Primary cilia are sensory organelles located at the cell surface. Their assembly is primed by centrosome migration to the apical surface, yet surprisingly little is known about this initiating step. To gain insight into the mechanisms driving centrosome migration, we exploited the reproducibility of cell architecture on adhesive micropatterns to investigate the cytoskeletal remodeling supporting it. Microtubule network densification and bundling, with the transient formation of an array of cold-stable microtubules, and actin cytoskeleton asymmetrical contraction participate in concert to drive apical centrosome migration. The distal appendage protein Cep164 appears to be a key actor involved in the cytoskeleton remodeling and centrosome migration, whereas intraflagellar transport 88's role seems to be restricted to axoneme elongation. Together, our data elucidate the hitherto unexplored mechanism of centrosome migration and show that it is driven by the increase and clustering of mechanical forces to push the centrosome toward the cell apical pole.