Septin 9 PB domains coordinate centrosome positioning and microtubule acetylation to control epithelial polarity
Abstract
Septins are cytoskeletal GTP-binding proteins that organize microtubules and scaffold polarity complexes. Here, we uncover a polybasic (PB)-domain-dependent mechanism by which septin 9 controls apico-basal polarity in epithelial cells. Septin 9 regulates centrosome positioning and the asymmetric distribution of acetylated microtubules, which are required for ciliogenesis and lumen formation. Knockdown of septin 9 or deletion of its PB domains disrupts centrosome asymmetry, induces a symmetric distribution of acetylated tubulin, and impairs cilia formation, leading to polarity inversion. These defects are associated with increased expression of the microtubule deacetylase HDAC6. Importantly, inhibition of TGF-β signaling or selective HDAC6 inhibition with tubacin restores microtubule acetylation and rescues apico-basal polarity. Together, our findings identify septin 9 as a cytoskeletal integrator that links centrosome positioning and microtubule acetylation to epithelial morphogenesis through the TGF-β/HDAC6 pathway.
Related
- NDE1 Localizes to the Subdistal Appendages to Maintain Centrosome Integrity and Microtubule Organization
- Microtubule lattice conformation and integrity regulate α-tubulin acetylation
- Intestinal epithelial Casd1 regulates mucus sialic acid O-acetylation and limits tissue damage from large-intestinal mucosal insults
- Planar cell polarity aligns epithelial migration to coordinate intestinal architecture and functional zonation
- Control of Golgi Architecture Through Three Centrosome Cohesion Pathways
BibTeX
@article{omrane2026septin,
title = {{Septin 9 PB domains coordinate centrosome positioning and microtubule acetylation to control epithelial polarity}},
author = {Mohyeddine Omrane and Nassima Benzoubir and Didier Samuel and Ama Gassama-Diagne},
journal = {FEBS Letters},
year = {2026},
month = may,
doi = {10.1002/1873-3468.70363},
url = {https://hal.science/hal-05840912v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Septin 9 PB domains coordinate centrosome positioning and microtubule acetylation to control epithelial polarity
AU - Mohyeddine Omrane
AU - Nassima Benzoubir
AU - Didier Samuel
AU - Ama Gassama-Diagne
PY - 2026
DA - 2026/05/26
JO - FEBS Letters
DO - 10.1002/1873-3468.70363
UR - https://hal.science/hal-05840912v1
AB - Septins are cytoskeletal GTP-binding proteins that organize microtubules and scaffold polarity complexes. Here, we uncover a polybasic (PB)-domain-dependent mechanism by which septin 9 controls apico-basal polarity in epithelial cells. Septin 9 regulates centrosome positioning and the asymmetric distribution of acetylated microtubules, which are required for ciliogenesis and lumen formation. Knockdown of septin 9 or deletion of its PB domains disrupts centrosome asymmetry, induces a symmetric distribution of acetylated tubulin, and impairs cilia formation, leading to polarity inversion. These defects are associated with increased expression of the microtubule deacetylase HDAC6. Importantly, inhibition of TGF-β signaling or selective HDAC6 inhibition with tubacin restores microtubule acetylation and rescues apico-basal polarity. Together, our findings identify septin 9 as a cytoskeletal integrator that links centrosome positioning and microtubule acetylation to epithelial morphogenesis through the TGF-β/HDAC6 pathway.
SN - 0014-5793
SN - 1873-3468
ER -