{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T02:43:05Z","timestamp":1775788985897,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01-DK-116352"],"award-info":[{"award-number":["R01-DK-116352"]}]},{"name":"National Institutes of Health","award":["UO1-DK-10316"],"award-info":[{"award-number":["UO1-DK-10316"]}]},{"name":"National Institutes of Health","award":["P30-DK-89502"],"award-info":[{"award-number":["P30-DK-89502"]}]},{"name":"National Institutes of Health","award":["CF-SINGH20G0"],"award-info":[{"award-number":["CF-SINGH20G0"]}]},{"name":"Hopkins Basic and Translational Research Digestive Diseases Research Core Center","award":["R01-DK-116352"],"award-info":[{"award-number":["R01-DK-116352"]}]},{"name":"Hopkins Basic and Translational Research Digestive Diseases Research Core Center","award":["UO1-DK-10316"],"award-info":[{"award-number":["UO1-DK-10316"]}]},{"name":"Hopkins Basic and Translational Research Digestive Diseases Research Core Center","award":["P30-DK-89502"],"award-info":[{"award-number":["P30-DK-89502"]}]},{"name":"Hopkins Basic and Translational Research Digestive Diseases Research Core Center","award":["CF-SINGH20G0"],"award-info":[{"award-number":["CF-SINGH20G0"]}]},{"name":"Cystic Fibrosis Foundation","award":["R01-DK-116352"],"award-info":[{"award-number":["R01-DK-116352"]}]},{"name":"Cystic Fibrosis Foundation","award":["UO1-DK-10316"],"award-info":[{"award-number":["UO1-DK-10316"]}]},{"name":"Cystic Fibrosis Foundation","award":["P30-DK-89502"],"award-info":[{"award-number":["P30-DK-89502"]}]},{"name":"Cystic Fibrosis Foundation","award":["CF-SINGH20G0"],"award-info":[{"award-number":["CF-SINGH20G0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholesterol-rich membrane domains, also called lipid rafts (LRs), are specialized membrane domains that provide a platform for intracellular signal transduction. Membrane proteins often cluster in LRs that further aggregate into larger platform-like structures that are enriched in ceramides and are called ceramide-rich platforms (CRPs). The role of CRPs in the regulation of intestinal epithelial functions remains unknown. Down-regulated in adenoma (DRA) is an intestinal Cl\u2212\/HCO3\u2212 antiporter that is enriched in LRs. However, little is known regarding the mechanisms involved in the regulation of DRA activity. The air\u2013liquid interface (ALI) was created by removing apical media for a specified number of days; from 12\u201314 days post-confluency, Caco-2\/BBe cells or a colonoid monolayer were grown as submerged cultures. Confocal imaging was used to examine the dimensions of membrane microdomains that contained DRA. DRA expression and activity were enhanced in Caco-2\/BBe cells and human colonoids using an ALI culture method. ALI causes an increase in acid sphingomyelinase (ASMase) activity, an enzyme responsible for enhancing ceramide content in the plasma membrane. ALI cultures expressed a larger number of DRA-containing platforms with dimensions &gt;2 \u00b5m compared to cells grown as submerged cultures. ASMase inhibitor, desipramine, disrupted CRPs and reduced the ALI-induced increase in DRA expression in the apical membrane. Exposing normal human colonoid monolayers to ALI increased the ASMase activity and enhanced the differentiation of colonoids along with basal and forskolin-stimulated DRA activities. ALI increases DRA activity and expression by increasing ASMase activity and platform formation in Caco-2\/BBe cells and by enhancing the differentiation of colonoids.<\/jats:p>","DOI":"10.3390\/ijms24098273","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T03:24:32Z","timestamp":1683257072000},"page":"8273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Air\u2013Liquid Interface Reorganizes Membrane Lipids and Enhances the Recruitment of Slc26a3 to Lipid-Rich Domains in Human Colonoid Monolayers"],"prefix":"10.3390","volume":"24","author":[{"given":"C. Ming","family":"Tse","sequence":"first","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine, School of Medicine, The Johns Hopkins University, 720 Rutland Avenue, 933 Ross Research Building, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9865-7135","authenticated-orcid":false,"given":"Zixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine, School of Medicine, The Johns Hopkins University, 720 Rutland Avenue, 933 Ross Research Building, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruxian","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine, School of Medicine, The Johns Hopkins University, 720 Rutland Avenue, 933 Ross Research Building, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafiquel","family":"Sarker","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine, School of Medicine, The Johns Hopkins University, 720 Rutland Avenue, 933 Ross Research Building, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Donowitz","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine, School of Medicine, The Johns Hopkins University, 720 Rutland Avenue, 933 Ross Research Building, Baltimore, MD 21205, USA"},{"name":"Department of Cellular and Molecular Physiology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varsha","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology & Hepatology, Department of Medicine, School of Medicine, The Johns Hopkins University, 720 Rutland Avenue, 933 Ross Research Building, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"C1279","DOI":"10.1152\/ajpcell.00638.2008","article-title":"Regulation of intestinal Cl\u2212\/HCO3\u2212 exchanger SLC26A3 by intracellular pH","volume":"296","author":"Hayashi","year":"2009","journal-title":"Am. 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