Microtubule stabilization drives 3D centrosome migration to initiate primary ciliogenesis

J Cell Biol. 2017 Nov 6;216(11):3713-3728. doi: 10.1083/jcb.201610039. Epub 2017 Oct 9.

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.

Publication types

  • Video-Audio Media
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / physiology*
  • Cell Line
  • Centrosome / metabolism
  • Centrosome / physiology*
  • Cilia / metabolism
  • Cilia / physiology
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology*
  • Humans
  • Mechanotransduction, Cellular
  • Microtubule Proteins / genetics
  • Microtubule Proteins / metabolism
  • Microtubules / metabolism
  • Microtubules / physiology*
  • Protein Stability
  • RNA Interference
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / physiology*
  • Time Factors
  • Transfection
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • CEP164 protein, human
  • IFT88 protein, human
  • Microtubule Proteins
  • Tumor Suppressor Proteins