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

Cell | 2017

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.

Pubmed ID: 28086093 RIS Download

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM095941
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM112988
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM118082
  • Agency: NIGMS NIH HHS, United States
    Id: DP2 GM105448
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR054396
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK102910

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