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.
Siew Cheng Phua  1 ,  Shuhei Chiba  2 ,  Masako Suzuki  3 ,  Emily Su  4 ,  Elle C Roberson  5 ,  Ganesh V Pusapati  6 ,  Stéphane Schurmans ,  Mitsutoshi Setou  7 ,  Rajat Rohatgi  6 ,  Jeremy F Reiter  5 ,  Koji Ikegami  8 ,  Takanari Inoue  9
Affiliations
  • 1. Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: [email protected].
  • 2. Laboratory of Biological Science, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
  • 3. Advanced Research Facilities and Services, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
  • 4. Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 5. Department of Biochemistry and Biophysics and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 6. Departments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 7. Department of Cellular and Molecular Anatomy and International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
  • 8. Department of Cellular and Molecular Anatomy and International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan. Electronic address: [email protected].
  • 9. Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: [email protected].
PMID: 28086093 DOI: 10.1016/j.cell.2016.12.032
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.

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.
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