Abstract: TH-PO0308
Regulation of Myo1e Localization in Epithelial Cells
Session Information
- Glomerular Diseases: Cell Biology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Amin, Sabrina, SUNY Upstate Medical University, Syracuse, New York, United States
- Loyd, Yoseph M., SUNY Upstate Medical University, Syracuse, New York, United States
- Krendel, Mira, SUNY Upstate Medical University, Syracuse, New York, United States
Background
Myosin 1e (Myo1e) is an actin-associated protein required for maintenance of glomerular filtration barrier integrity. Mutations in Myo1e disrupt myosin localization to podocyte cell-cell contacts and are associated with familial glomerular disease, highlighting the importance of proper Myo1e localization at specialized epithelial membrane domains. The mechanisms regulating Myo1e membrane recruitment and spatial distribution remain poorly understood. Using polarized epithelial cells (MDCK) as an experimental framework for studying membrane domain organization, we analyzed pathways regulating Myo1e localization.
Methods
Myo1e localization was analyzed in MDCK cells by confocal microscopy under varying states of epithelial organization, including subconfluent islands and polarized monolayers grown on Transwell supports. PI3K signaling was inhibited using LY294002 to examine phosphoinositide-dependent regulation of Myo1e membrane targeting. Regulation by protein-protein interactions was investigated through overexpression of OSTF1, a protein that binds Myo1e tail domain. Quantitative image analysis of confocal Z-stacks was used to measure Myo1e distribution, with Myo1e intensity quantified along junction-associated or leading edge-localized regions of interest and compared with adjacent cytoplasmic regions.
Results
Myo1e preferentially localized to cell-cell contacts and showed minimal enrichment at free cell edges. In polarized monolayers, junctional localization of Myo1e was strongest during early/intermediate stages of monolayer maturation and was reduced in mature, highly polarized cultures, indicating dynamic regulation during epithelial maturation. PI3K inhibition reduced Myo1e enrichment at cell-cell contacts, supporting a role for phosphoinositide signaling in Myo1e recruitment. In addition, expression of non-phosphorylatable OSTF1, which strongly binds Myo1e, decreased junctional Myo1e localization, whereas wild-type OSTF1 had minimal effect.
Conclusion
These findings identify PI3K-dependent signaling and OSTF1-mediated regulation as mechanisms controlling Myo1e localization in epithelial cells. Our results support a model in which Myo1e is dynamically recruited to specialized junctional membrane domains through regulated tail-domain interactions. Because podocyte integrity depends on stable junctional organization, disruption of Myo1e membrane targeting may contribute to glomerular barrier dysfunction and kidney disease.
Funding
- NIDDK Support