bioRxiv preprint doi: https://doi.org/10.1101/2021.07.05.451173; this version posted July 5, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Exocyst Inactivation in Urothelial Cells Disrupts Autophagy and Activates non-canonical NF-κB Michael A. Ortega1,2, Ross K. Villiger2, Malia Harrison-Chau2, Suzanna Lieu2, Kadee-Kalia Tamashiro2, Amanda J. Lee2,3, Brent A. Fujimoto2, Geetika Y. Patwardhan2, Joshua Kepler2 & Ben Fogelgren*2 1 Center for Biomedical Research at The Queen’s Medical Center, Honolulu, Hawaii 96813; 2 Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813; 3 Math and Sciences Department, Kapiolani Community College, Honolulu, Hawaii 96816. *Corresponding Author: Ben Fogelgren Email address:
[email protected] Keywords: autophagy / exocyst / Fn14 / NF-κB / urothelium 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.07.05.451173; this version posted July 5, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have reported that ureteric bud-specific ablation of the exocyst Exoc5 subunit in late-murine gestation results in failure of urothelial stratification, cell death, and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death, and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development.