title: Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision.
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.
authors.affiliation: 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.
authors.forename: Siew Cheng
authors.initials: SC
authors.lastname: Phua
authors.affiliation: Laboratory of Biological Science, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Advanced Research Facilities and Services, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Su
authors.affiliation: Department of Biochemistry and Biophysics and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Elle C
authors.initials: EC
authors.lastname: Roberson
authors.affiliation: Departments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Pusapati
authors.forename: Stéphane
authors.initials: S
authors.lastname: Schurmans
authors.affiliation: Department of Cellular and Molecular Anatomy and International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.affiliation: Departments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Rohatgi
authors.affiliation: Department of Biochemistry and Biophysics and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jeremy F
authors.initials: JF
authors.lastname: Reiter
authors.affiliation: 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.
authors.forename: Koji
authors.initials: K
authors.lastname: Ikegami
authors.affiliation: Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jctinoue@jhmi.edu.
authors.forename: Takanari
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle; D002923:Cilia / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D019269:Phosphatidylinositol 4,5-Diphosphate; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism; D000099182:Phosphoinositide 5-Phosphatases
chemical_list: D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010744:Phosphoric Monoester Hydrolases; D000071676:Zinc Finger Protein GLI1; D000099182:Phosphoinositide 5-Phosphatases; C498520:Gli1 protein, mouse
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