{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:58:30Z","timestamp":1787018310798,"version":"build-2736575974"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The regulation of microtubule dynamics in cystic fibrosis (CF) epithelial cells and the consequences of reduced rates of microtubule polymerization on downstream CF cellular events, such as cholesterol accumulation, a marker of impaired intracellular transport, are explored here. It is identified that microtubules in both CF cell models and in primary CF nasal epithelial cells repolymerize at a slower rate compared with respective controls. Previous studies suggest a role for cAMP in modulating organelle transport in CF cells, implicating a role for exchange protein activated by cAMP (EPAC) 1, a regulator of microtubule elongation, as a potential mechanism. EPAC1 activity is reduced in CF cell models and in Cftr\u2212\/\u2212 mouse lung compared with respective non-CF controls. Stimulation of EPAC1 activity with the selective EPAC1 agonist, 8-cpt-2-O-Me-cAMP, stimulates microtubule repolymerization to wild-type rates in CF cells. EPAC1 activation also alleviates cholesterol accumulation in CF cells, suggesting a direct link between microtubule regulation and intracellular transport. To verify the relationship between transport and microtubule regulation, expression of the protein, tubulin polymerization\u2013promoting protein, was knocked down in non-CF human tracheal (9\/HTEo\u2212) cells to mimic the microtubule dysregulation in CF cells. Transduced cells with short hairpin RNA targeting tubulin polymerization\u2013promoting protein exhibit CF-like perinuclear cholesterol accumulation and other cellular manifestations of CF cells, thus supporting a role for microtubule regulation as a mechanism linking CFTR function to downstream cellular manifestation.<\/jats:p>","DOI":"10.1165\/rcmb.2014-0462oc","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T14:55:47Z","timestamp":1431096947000},"page":"853-862","source":"Crossref","is-referenced-by-count":21,"title":["Role of Exchange Protein Activated by cAMP 1 in Regulating Rates of Microtubule Formation in Cystic Fibrosis Epithelial Cells"],"prefix":"10.1093","volume":"53","author":[{"given":"Sharon M.","family":"Rymut","sequence":"first","affiliation":[{"name":"Departments of Pharmacology"},{"name":"Pediatrics, 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