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Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision.
Siew Cheng Phua1, Shuhei Chiba2, Masako Suzuki3
1Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cell
|January 14, 2017
Summary
Primary cilia dynamics are regulated by Inpp5e, an enzyme that controls actin polymerization. This process, called cilia decapitation, leads to cilia disassembly and may link cell division to cancer development.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Primary cilia are crucial signaling hubs in quiescent cells.
- Their structural dynamics are tightly regulated.
- The mechanisms controlling primary cilium disassembly are not fully understood.
Purpose of the Study:
- To investigate the role of Inpp5e in regulating primary cilium structure and dynamics.
- To elucidate the mechanism of primary cilium disassembly.
- To explore the link between primary cilia and cell cycle progression.
Main Methods:
- Utilized cell culture models and live-cell imaging.
- Employed biochemical assays to analyze protein localization and lipid modifications.
- Investigated the role of Inpp5e using genetic manipulation and pharmacological inhibitors.
Main Results:
- Demonstrated that Inpp5e restricts ciliary structure dynamics in quiescent cells.
- Showed that growth induction leads to Inpp5e displacement and phosphatidylinositol 4,5-bisphosphate accumulation in distal cilia.
- Identified a novel mechanism of cilia disassembly termed 'cilia decapitation,' involving actin polymerization and excision of cilia tips.
- Revealed that cilia decapitation precedes resorption and involves acute loss of intraflagellar transport B (IFT-B).
Conclusions:
- Cilia decapitation is a newly defined mechanism for primary cilium disassembly.
- This process links the primary cilium life cycle to the cell-division cycle by inducing mitogenic signaling.
- The findings suggest a role for cilia decapitation in cell proliferation control, with potential implications for development and cancer.
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