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

Cell. 2017 Jan 12;168(1-2):264-279.e15. doi: 10.1016/j.cell.2016.12.032. Epub 2017 Jan 12.


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.

Keywords: AurA; F-actin; Gli; Inpp5e; PI(4,5)P(2); Primary cilia; cell-cycle entry; decapitation; disassembly; ectosome; extracellular vesicles; genetically encoded ciliary actin inhibitor.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Cycle*
  • Cilia / metabolism*
  • Kidney / cytology
  • Kidney / metabolism
  • Mice
  • NIH 3T3 Cells
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphoric Monoester Hydrolases / metabolism
  • Zinc Finger Protein GLI1 / metabolism


  • Actins
  • Gli1 protein, mouse
  • Phosphatidylinositol 4,5-Diphosphate
  • Zinc Finger Protein GLI1
  • Phosphoric Monoester Hydrolases
  • phosphoinositide 5-phosphatase