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Updated: Jun 13, 2026
09:09
Bottom-Up In Vitro Methods to Assay the Ultrastructural Organization, Membrane Reshaping, and Curvature Sensitivity Behavior of Septins
Published on: August 17, 2022
Septins regulate kinase-inhibitor induced micron-scale vacuolation
Khushboo Sharma1, Himanshi Sharma1, Janki Insan1
1Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, 110016, India.
Experimental Cell Research
|June 11, 2026
Summary
Septin inhibitor Forchlorfenuron (FCF) was identified as a novel modulator of micron-scale vacuolation, a process linked to endosomal pathways. FCF suppresses vacuole formation and resolution, suggesting septins play a key role in endosome maturation.
Area of Science:
- Cell Biology
- Molecular Pharmacology
Background:
- Kinase inhibitors targeting pathways like p38 MAPK and PIKFYVE can induce endosomal swelling and micron-scale vacuolation.
- The precise mechanisms and cellular components involved in this vacuolation process are not fully understood.
Purpose of the Study:
- To identify small molecule modulators of kinase inhibitor-induced micron-scale vacuolation.
- To elucidate the role of septins in the formation and resolution of these vacuoles.
Main Methods:
- Conducted a small molecule screen to identify vacuolation inhibitors.
- Utilized shRNA to deplete specific septin proteins (SEPT9, SEPT7).
- Characterized vacuole morphology and localization using immunofluorescence microscopy (RAB7, CD63).
Main Results:
- Identified Forchlorfenuron (FCF), a septin inhibitor, as a potent suppressor of vacuolation induced by various kinase inhibitors.
- SEPT9 depletion abrogated kinase inhibitor-induced vacuolation, while SEPT7 depletion had no effect.
- FCF treatment led to the loss of RAB7+ late endosomes and suppressed vacuole resolution, independent of autophagy pathways.
Conclusions:
- Septins, particularly SEPT9, play a critical role in regulating micron-scale vacuolation, likely through their involvement in endosome maturation.
- FCF represents a novel tool for studying endosomal dynamics and the function of septins in cellular processes.
- Septin involvement may contribute to the cell-type specific nature of micron-scale vacuolation.
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