Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision

Siew Cheng Phua, Shuhei Chiba, Masako Suzuki, Emily Su, Elle C. Roberson, Ganesh V. Pusapati, Mitsutoshi Setou, Rajat Rohatgi, Jeremy F. Reiter, Koji Ikegami, Takanari Inoue

Research output: Contribution to journalArticle

Abstract

The life cycle of a primary cilium begins in quiescence and ends prior to mitosis. In quiescent cells, the primary cilium insulates itself from contiguous dynamic membrane processes on the cell surface to function as a stable signaling apparatus. Here, we demonstrate that basal restriction of ciliary structure dynamics is established by the cilia-enriched phosphoinositide 5-phosphatase, Inpp5e. Growth induction displaces ciliary Inpp5e and accumulates phosphatidylinositol 4,5-bisphosphate in distal cilia. This change triggers otherwise-forbidden actin polymerization in primary cilia, which excises cilia tips in a process we call cilia decapitation. While cilia disassembly is traditionally thought to occur solely through resorption, we show that an acute loss of IFT-B through cilia decapitation precedes resorption. Finally, we propose that cilia decapitation induces mitogenic signaling and constitutes a molecular link between the cilia life cycle and cell-division cycle. This newly defined ciliary mechanism may find significance in cell proliferation control during normal development and cancer.

Original languageEnglish (US)
Pages (from-to)264-279.e15
JournalCell
Volume168
Issue number1-2
DOIs
StatePublished - Jan 12 2017

Keywords

  • AurA
  • F-actin
  • Gli
  • Inpp5e
  • PI(4,5)P
  • Primary cilia
  • cell-cycle entry
  • decapitation
  • disassembly
  • ectosome
  • extracellular vesicles
  • genetically encoded ciliary actin inhibitor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Phua, S. C., Chiba, S., Suzuki, M., Su, E., Roberson, E. C., Pusapati, G. V., Setou, M., Rohatgi, R., Reiter, J. F., Ikegami, K., & Inoue, T. (2017). Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision. Cell, 168(1-2), 264-279.e15. https://doi.org/10.1016/j.cell.2016.12.032