{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:47:03Z","timestamp":1789447623354,"version":"build-2803163510"},"reference-count":68,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK117308"],"award-info":[{"award-number":["R01DK117308"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P20GM103456-06A1-8293"],"award-info":[{"award-number":["P20GM103456-06A1-8293"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R03DK100738"],"award-info":[{"award-number":["R03DK100738"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000912","name":"March of Dimes Foundation","doi-asserted-by":"crossref","award":["5-FY14-56"],"award-info":[{"award-number":["5-FY14-56"]}],"id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ureter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have previously reported that ureteric bud-specific ablation of the gene expressing the exocyst subunit EXOC5 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. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-\u03baB stress response. Impaired autophagy first provokes canonical NF-\u03baB activity, which is progressively followed by increasing levels of non-canonical NF-\u03baB activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of the pan-caspase inhibitor z-VAD-FMK at embryonic day 16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-\u03baB signaling, which promotes obstructive uropathy.<\/jats:p>","DOI":"10.1242\/dmm.049785","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T05:09:32Z","timestamp":1661404172000},"source":"Crossref","is-referenced-by-count":6,"title":["Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-\u03baB signaling"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3669-8266","authenticated-orcid":false,"given":"Michael A.","family":"Ortega","sequence":"first","affiliation":[{"name":"Center for Biomedical Research at The Queen's Medical Center 1 , Honolulu, Hawaii 96813 , USA"},{"name":"University of Hawai\u02bfi at Manoa 2 Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine , , Honolulu, Hawaii 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross K.","family":"Villiger","sequence":"additional","affiliation":[{"name":"University of Hawai\u02bfi at Manoa 2 Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine , , Honolulu, Hawaii 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1280-5370","authenticated-orcid":false,"given":"Malia","family":"Harrison-Chau","sequence":"additional","affiliation":[{"name":"University of Hawai\u02bfi at Manoa 2 Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine , , Honolulu, Hawaii 96813 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanna","family":"Lieu","sequence":"additional","affiliation":[{"name":"University of Hawai\u02bfi at Manoa 2 Department of Anatomy, Biochemistry and Physiology, John A. 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