2. Academic Validation
  3. Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision

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

Affiliations

  • 1 Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: phua0022@e.ntu.edu.sg.
  • 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: kikegami@hama-med.ac.jp.
  • 9 Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jctinoue@jhmi.edu.
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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