Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors

Nat Cell Biol. 2011 Apr;13(4):402-11. doi: 10.1038/ncb2218. Epub 2011 Mar 13.

Abstract

Primary cilia are displayed during the G(0)/G(1) phase of many cell types. Cilia are resorbed as cells prepare to re-enter the cell cycle, but the causal and molecular link between these two cellular events remains unclear. We show that Tctex-1 phosphorylated at Thr 94 is recruited to ciliary transition zones before S-phase entry and has a pivotal role in both ciliary disassembly and cell cycle progression. However, the role of Tctex-1 in S-phase entry is dispensable in non-ciliated cells. Exogenously adding a phospho-mimic Tctex-1(T94E) mutant accelerates cilium disassembly and S-phase entry. These results support a model in which the cilia act as a brake to prevent cell cycle progression. Mechanistic studies show the involvement of actin dynamics in Tctex-1-regulated cilium resorption. Tctex-1 phosphorylated at Thr 94 is also selectively enriched at the ciliary transition zones of cortical neural progenitors, and has a key role in controlling G(1) length, cell cycle entry and fate determination of these cells during corticogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology
  • Cell Line
  • Cerebral Cortex / cytology
  • Cerebral Cortex / growth & development
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Dyneins / genetics
  • Dyneins / metabolism*
  • Humans
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / physiology*
  • Neuroglia / cytology
  • Neuroglia / physiology
  • Phosphorylation
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • S Phase / physiology*

Substances

  • DYNLT1 protein, human
  • Recombinant Fusion Proteins
  • Dyneins