{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:37:40Z","timestamp":1786451860937,"version":"build-2736575974"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004238","name":"Universit\u00e4t Potsdam","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004238","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Zinc (Zn) deficiency affects approximately 1\u00a0billion people worldwide with severe consequences for their health, including increased intestinal infections, inflammation, and diarrhea. Accordingly, the intestinal defense barrier is compromised, leading to epithelial destruction and alteration of mucus. However, the processes and the extent to which Zn deficiency affects mucin synthesis in intestinal goblet cells (GCs) remain poorly understood. To this end, we investigated the impact of Zn deficiency on mucin expression and glycosylation in the human GC model HT-29-MTX. Zn deprivation altered the GC transcriptome, affecting genes involved in Zn transport, mucin synthesis and glycosylation. Accordingly, mucus composition was changed in Zn-deficient GCs, significantly increasing MUC2 and MUC17 on the mRNA and protein level. Several Zn transporters, mostly those associated with the early secretory pathway (ESP), were dysregulated, indicating an adaptive response of cellular Zn homeostasis. Additionally, free Zn was markedly reduced in the ESP, a critical location for glycosylation. Zn deficit substantially changed mucin glycosylation, characterized by an increase in sialylation and a strong decrease in complex\n                    <jats:italic>N<\/jats:italic>\n                    -glycans. All these changes involved widespread dysregulation of glycosyltransferase expression, including an increase in COSMC, a Zn-binding chaperone essential for the core 1\n                    <jats:italic>O<\/jats:italic>\n                    -glycan formation. Collectively, our in vitro findings demonstrate that Zn is a critical regulator of mucin production and glycosylation in GCs. Zn deficiency might weaken the protective and functional qualities of intestinal mucus, increasing the risk of infections and potentially disrupting host-microbiome interactions.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-66227-4","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T23:16:06Z","timestamp":1786403766000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptome, glycome, and mucinome analysis reveal zinc is essential for the composition of mucus in the human goblet cell model HT-29-MTX"],"prefix":"10.1038","volume":"16","author":[{"given":"Christoph","family":"Sch\u00fc\u00dfler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nara","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"L\u00e9onard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Sprenger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tari","family":"R\u00f6del","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keira E.","family":"Mahoney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Ocket","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Matthaeus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Denis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Ebert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willy","family":"Morelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Foulquier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Braeuning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Robbe","family":"Masselot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy A.","family":"Malaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9140-2448","authenticated-orcid":false,"given":"Maria","family":"Maares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"66227_CR1","doi-asserted-by":"publisher","first-page":"1478S","DOI":"10.3945\/ajcn.2010.28674I","volume":"91","author":"KM Hambidge","year":"2010","unstructured":"Hambidge, K. M., Miller, L. V., Westcott, J. E., Sheng, X. & Krebs, N. F. Zinc bioavailability and homeostasis. Am. J. Clin. Nutr. 91, 1478S\u20131483S (2010).","journal-title":"Am. J. Clin. Nutr."},{"key":"66227_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.advnut.2024.100181","volume":"15","author":"NM Lowe","year":"2024","unstructured":"Lowe, N. M. et al. Preventing and controlling zinc deficiency across the life course: A call to action. Adv. Nutr. 15, 100181 (2024).","journal-title":"Adv. Nutr."},{"key":"66227_CR3","doi-asserted-by":"publisher","first-page":"762","DOI":"10.3390\/nu12030762","volume":"12","author":"M Maares","year":"2020","unstructured":"Maares, M. & Haase, H. A guide to human zinc absorption: General overview and recent advances of in vitro intestinal models. Nutrients 12, 762 (2020).","journal-title":"Nutrients"},{"key":"66227_CR4","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.2741\/Corfield","volume":"6","author":"AP Corfield","year":"2001","unstructured":"Corfield, A. P., Carroll, D., Myerscough, N. & Probert, C. S. J. Mucins in the gastrointestinal tract in health and disease. Front. Biosci. 6, 1321\u20131357 (2001).","journal-title":"Front. Biosci."},{"key":"66227_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2024.127459","volume":"84","author":"V Einhorn","year":"2024","unstructured":"Einhorn, V., Haase, H. & Maares, M. Interaction and competition for intestinal absorption by zinc, iron, copper, and manganese at the intestinal mucus layer. J. Trace Elem. Med. Biol. 84, 127459 (2024).","journal-title":"J. Trace Elem. Med. Biol."},{"key":"66227_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092662","volume":"19","author":"M Maares","year":"2018","unstructured":"Maares, M. et al. In vitro studies on zinc binding and buffering by intestinal mucins. Int. J. Mol. Sci. 19, 2662 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"66227_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2025.109983","volume":"144","author":"M Maares","year":"2025","unstructured":"Maares, M. et al. Investigation of competitive binding of the essential trace elements zinc, iron, copper, and manganese by gastrointestinal mucins and the effect on their absorption in vitro. J. Nutr. Biochem. 144, 109983 (2025).","journal-title":"J. Nutr. Biochem."},{"key":"66227_CR8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.addr.2017.09.023","volume":"124","author":"R Bansil","year":"2018","unstructured":"Bansil, R. & Turner, B. S. The biology of mucus: Composition, synthesis and organization. Adv. Drug Deliv. Rev. 124, 3\u201315 (2018).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"66227_CR9","doi-asserted-by":"publisher","first-page":"3635","DOI":"10.1007\/s00018-011-0822-3","volume":"68","author":"MEV Johansson","year":"2011","unstructured":"Johansson, M. E. V. et al. Composition and functional role of the mucus layers in the intestine. Cell. Mol. Life Sci. 68, 3635\u20133641 (2011).","journal-title":"Cell. Mol. Life Sci."},{"key":"66227_CR10","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/s41581-019-0129-4","volume":"15","author":"C Reily","year":"2019","unstructured":"Reily, C., Stewart, T. J., Renfrow, M. B. & Novak, J. Glycosylation in health and disease. Nat. Rev. Nephrol. 15, 346\u2013366 (2019).","journal-title":"Nat. Rev. Nephrol."},{"key":"66227_CR11","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/nrmicro2746","volume":"10","author":"NM Koropatkin","year":"2012","unstructured":"Koropatkin, N. M., Cameron, E. A. & Martens, E. C. How glycan metabolism shapes the human gut microbiota. Nat. Rev. Microbiol. 10, 323\u2013335 (2012).","journal-title":"Nat. Rev. Microbiol."},{"key":"66227_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/biom15111552","volume":"15","author":"Y Li","year":"2025","unstructured":"Li, Y., Pan, J., Liu, H. & Liu, C. Intestinal mucin glycosylation: Structural regulation, homeostasis maintenance and disease association. Biomolecules 15, 1552 (2025).","journal-title":"Biomolecules"},{"key":"66227_CR13","doi-asserted-by":"publisher","first-page":"G452","DOI":"10.1152\/ajpgi.00261.2022","volume":"324","author":"E Fekete","year":"2023","unstructured":"Fekete, E. & Buret, A. G. The role of mucin O-glycans in microbiota dysbiosis, intestinal homeostasis, and host-pathogen interactions. Am. J. Physiol. Gastrointest. Liver Physiol. 324, G452\u2013G465 (2023).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"66227_CR14","doi-asserted-by":"publisher","first-page":"3613","DOI":"10.1093\/bioinformatics\/btaa190","volume":"36","author":"AY Mehta","year":"2020","unstructured":"Mehta, A. Y. & Cummings, R. D. GlycoGlyph: A glycan visualizing, drawing and naming application. Bioinformatics 36, 3613\u20133614 (2020).","journal-title":"Bioinformatics"},{"key":"66227_CR15","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/0024-3205(76)90288-5","volume":"19","author":"J Quarterman","year":"1976","unstructured":"Quarterman, J., Jackson, F. A. & Morrison, J. N. The effect of zinc deficiency on sheep intestinal mucin. Life Sci. 19, 979\u2013986 (1976).","journal-title":"Life Sci."},{"key":"66227_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176149","volume":"21","author":"M Maares","year":"2020","unstructured":"Maares, M., Keil, C., Straubing, S., Robbe-Masselot, C. & Haase, H. Zinc deficiency disturbs mucin expression, O-glycosylation and secretion by intestinal goblet cells. Int. J. Mol. Sci. 21, 6149 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"66227_CR17","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-6222474\/v1","author":"A Roy","year":"2025","unstructured":"Roy, A. et al. N-glycosylation enzyme Mpi is essential for mucin O-glycosylation, host-microbe homeostasis, Paneth cell defense, and metabolism. Res. Sq. https:\/\/doi.org\/10.21203\/rs.3.rs-6222474\/v1 (2025).","journal-title":"Res. Sq."},{"issue":"9","key":"66227_CR18","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1093\/glycob\/cwad003","volume":"33","author":"TB R\u00f8mer","year":"2023","unstructured":"R\u00f8mer, T. B. et al. CRISPR-screen identifies ZIP9 and dysregulated Zn2\u2009+\u2009homeostasis as a cause of cancer-associated changes in glycosylation. Glycobiology 33(9), 700\u2013714 (2023).","journal-title":"Glycobiology"},{"key":"66227_CR19","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.isci.2019.05.005","volume":"15","author":"T Yamaji","year":"2019","unstructured":"Yamaji, T. et al. A CRISPR screen using subtilase cytotoxin identifies SLC39A9 as a glycan-regulating factor. iScience 15, 407\u2013420 (2019).","journal-title":"iScience"},{"key":"66227_CR20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0239681","volume":"15","author":"ME Kable","year":"2020","unstructured":"Kable, M. E. et al. The Znt7-null mutation has sex dependent effects on the gut microbiota and goblet cell population in the mouse colon. PLoS One 15, e0239681 (2020).","journal-title":"PLoS One"},{"key":"66227_CR21","doi-asserted-by":"publisher","first-page":"4096","DOI":"10.1074\/jbc.M207644200","volume":"278","author":"CP Kirschke","year":"2003","unstructured":"Kirschke, C. P. & Huang, L. ZnT7, a novel mammalian zinc transporter, accumulates zinc in the golgi apparatus. J. Biol. Chem. 278, 4096\u20134102 (2003).","journal-title":"J. Biol. Chem."},{"issue":"6","key":"66227_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107378","volume":"300","author":"H Yuasa","year":"2024","unstructured":"Yuasa, H. et al. ZNT5-6 and ZNT7 play an integral role in protein N-glycosylation by supplying Zn2+ to Golgi \u03b1-mannosidase II. J. Biol. Chem. 300(6), 107378 (2024).","journal-title":"J. Biol. Chem."},{"key":"66227_CR23","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/1479-7364-5-3-170","volume":"5","author":"RL Smathers","year":"2011","unstructured":"Smathers, R. L. & Petersen, D. R. The human fatty acid-binding protein family: Evolutionary divergences and functions. Hum. Genomics. 5, 170\u2013191 (2011).","journal-title":"Hum. Genomics"},{"key":"66227_CR24","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.clinbiochem.2021.03.003","volume":"92","author":"H-Y Liao","year":"2021","unstructured":"Liao, H.-Y., Da, C.-M., Liao, B. & Zhang, H.-H. Roles of matrix metalloproteinase-7 (MMP-7) in cancer. Clin. Biochem. 92, 9\u201318 (2021).","journal-title":"Clin. Biochem."},{"key":"66227_CR25","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1007\/978-4-431-54240-7_10","volume-title":"Handbook of Glycosyltransferases and Related Genes","author":"AV Nairn","year":"2014","unstructured":"Nairn, A. V. & Moremen, K. W. Mannosyl-Oligosaccharide Glucosidase (Glucosidase I, MOGS). In Handbook of Glycosyltransferases and Related Genes (ed. Taniguchi, N.) 1273\u20131282 (2014)."},{"key":"66227_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25137279","volume":"25","author":"L Chen","year":"2024","unstructured":"Chen, L. et al. GAL3ST1 deficiency reduces epithelial\u2013mesenchymal transition and tumorigenic capacity in a cholangiocarcinoma cell line. Int. J. Mol. Sci. 25, 7279 (2024).","journal-title":"Int. J. Mol. Sci."},{"key":"66227_CR27","doi-asserted-by":"publisher","first-page":"3585","DOI":"10.1016\/j.cell.2024.04.041","volume":"187","author":"MP Wilson","year":"2024","unstructured":"Wilson, M. P. et al. A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis. Cell 187, 3585\u20133601 (2024).","journal-title":"Cell"},{"key":"66227_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31062-4","volume":"13","author":"SA Malaker","year":"2022","unstructured":"Malaker, S. A. et al. Revealing the human mucinome. Nat. Commun. 13, 3542 (2022).","journal-title":"Nat. Commun."},{"key":"66227_CR29","doi-asserted-by":"publisher","first-page":"6817","DOI":"10.3748\/wjg.v23.i37.6817","volume":"23","author":"MT Cairns","year":"2017","unstructured":"Cairns, M. T. et al. Glycosylation-related gene expression in HT29-MTX-E12 cells upon infection by Helicobacter pylori. World J. Gastroenterol. 23, 6817\u20136832 (2017).","journal-title":"World J. Gastroenterol."},{"key":"66227_CR30","doi-asserted-by":"publisher","first-page":"13944","DOI":"10.1074\/jbc.M210069200","volume":"278","author":"ME Lidell","year":"2003","unstructured":"Lidell, M. E., Johansson, M. E. V. & Hansson, G. C. An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. J. Biol. Chem. 278, 13944\u201313951 (2003).","journal-title":"J. Biol. Chem."},{"key":"66227_CR31","doi-asserted-by":"publisher","first-page":"fiaf066","DOI":"10.1093\/femsec\/fiaf066","volume":"101","author":"C de Ram","year":"2025","unstructured":"de Ram, C. et al. Distinct in vitro utilization and degradation of porcine gastric mucin glycans by human intestinal bacteria. FEMS Microbiol. Ecol. 101, fiaf066 (2025).","journal-title":"FEMS Microbiol. Ecol."},{"key":"66227_CR32","doi-asserted-by":"publisher","first-page":"14787","DOI":"10.1073\/pnas.1612158114","volume":"113","author":"MR Kudelka","year":"2016","unstructured":"Kudelka, M. R. et al. Cosmc is an X-linked inflammatory bowel disease risk gene that spatially regulates gut microbiota and contributes to sex-specific risk. Proc. Natl. Acad. Sci. 113, 14787\u201314792 (2016).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"66227_CR33","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1023\/A:1010974909998","volume":"18","author":"I Behrens","year":"2001","unstructured":"Behrens, I., Stenberg, P., Artursson, P. & Kissel, T. Transport of lipophilic drug molecules in a new mucus-secreting cell culture model based on HT29-MTX cells. Pharm. Res. 18, 1138\u20131145 (2001).","journal-title":"Pharm. Res."},{"key":"66227_CR34","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1006\/excr.1997.3638","volume":"235","author":"S Hennebicq-Reig","year":"1997","unstructured":"Hennebicq-Reig, S. et al. O-glycosylation and cellular differentiation in a subpopulation of mucin-secreting HT-29 cell line. Exp. Cell. Res. 235, 100\u2013107 (1997).","journal-title":"Exp. Cell. Res."},{"key":"66227_CR35","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3390\/biology9120468","volume":"9","author":"M Maares","year":"2020","unstructured":"Maares, M. et al. Time- and zinc-related changes in biomechanical properties of human colorectal cancer cells examined by atomic force microscopy. Biology 9, 468 (2020).","journal-title":"Biology"},{"issue":"1","key":"66227_CR36","doi-asserted-by":"publisher","first-page":"4070","DOI":"10.1038\/s41467-021-24366-4","volume":"12","author":"R Nason","year":"2021","unstructured":"Nason, R. et al. Display of the human mucinome with defined O-glycans by gene engineered cells. Nat. Commun. 124070. (2021).","journal-title":"Nat. Commun."},{"key":"66227_CR37","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1042\/BCJ20190180","volume":"476","author":"H Schneider","year":"2019","unstructured":"Schneider, H. et al. The human transmembrane mucin MUC17 responds to TNF\u03b1 by increased presentation at the plasma membrane. Biochem. J. 476, 2281\u20132295 (2019).","journal-title":"Biochem. J."},{"key":"66227_CR38","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.261468","volume":"137","author":"C Segui-Perez","year":"2024","unstructured":"Segui-Perez, C. et al. MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C. J. Cell Sci. 137, jcs261468 (2024).","journal-title":"J. Cell Sci."},{"key":"66227_CR39","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1093\/jn\/138.9.1664","volume":"138","author":"A Finamore","year":"2008","unstructured":"Finamore, A., Massimi, M., Conti Devirgiliis, L. & Mengheri, E. Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in Caco-2 Cells1. J. Nutr. 138, 1664\u20131670 (2008).","journal-title":"J. Nutr."},{"key":"66227_CR40","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1039\/c1mt00064k","volume":"3","author":"DJ Eide","year":"2011","unstructured":"Eide, D. J. The oxidative stress of zinc deficiency. Metallomics 3, 1124\u20131129 (2011).","journal-title":"Metallomics"},{"key":"66227_CR41","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jnutbio.2012.06.007","volume":"24","author":"I Wessels","year":"2013","unstructured":"Wessels, I., Haase, H., Engelhardt, G., Rink, L. & Uciechowski, P. Zinc deficiency induces production of the proinflammatory cytokines IL-1\u03b2 and TNF\u03b1 in promyeloid cells via epigenetic and redox-dependent mechanisms. J. Nutr. Biochem. 24, 289\u2013297 (2013).","journal-title":"J. Nutr. Biochem."},{"key":"66227_CR42","doi-asserted-by":"publisher","first-page":"6236","DOI":"10.4049\/jimmunol.0900614","volume":"183","author":"T Fujisawa","year":"2009","unstructured":"Fujisawa, T. et al. Regulation of airway MUC5AC expression by IL-1\u03b2 and IL-17A; The NF-\u03baB paradigm. J. Immunol. 183, 6236\u20136243 (2009).","journal-title":"J. Immunol."},{"key":"66227_CR43","doi-asserted-by":"publisher","first-page":"15686","DOI":"10.1074\/jbc.RA119.010227","volume":"294","author":"Y Nishito","year":"2019","unstructured":"Nishito, Y. & Kambe, T. Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels. J. Biol. Chem. 294, 15686\u201315697 (2019).","journal-title":"J. Biol. Chem."},{"key":"66227_CR44","doi-asserted-by":"publisher","first-page":"6992","DOI":"10.1074\/jbc.M610552200","volume":"282","author":"X Mao","year":"2007","unstructured":"Mao, X., Kim, B. E., Wang, F., Eide, D. J. & Petris, M. J. A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. J. Biol. Chem. 282, 6992\u20137000 (2007).","journal-title":"J. Biol. Chem."},{"key":"66227_CR45","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1515\/BC.2007.149","volume":"388","author":"BP Weaver","year":"2007","unstructured":"Weaver, B. P., Dufner-Beattie, J., Kambe, T. & Andrews, G. K. Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5). bchm 388, 1301\u20131312 (2007).","journal-title":"bchm"},{"key":"66227_CR46","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1042\/BST0361242","volume":"36","author":"GK Andrews","year":"2008","unstructured":"Andrews, G. K. Regulation and function of Zip4, the acrodermatitis enteropathica gene. Biochem. Soc. Trans. 36, 1242\u20131246 (2008).","journal-title":"Biochem. Soc. Trans."},{"key":"66227_CR47","doi-asserted-by":"publisher","first-page":"4841","DOI":"10.1073\/pnas.95.9.4841","volume":"95","author":"RJ McMahon","year":"1998","unstructured":"McMahon, R. J. & Cousins, R. J. Regulation of the zinc transporter ZnT-1 by dietary zinc. Proc. Natl. Acad. Sci. 95, 4841\u20134846 (1998).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"66227_CR48","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1002\/iub.291","volume":"62","author":"X Wang","year":"2010","unstructured":"Wang, X. & Zhou, B. Dietary zinc absorption: A play of Zips and ZnTs in the gut. IUBMB Life. 62, 176\u2013182 (2010).","journal-title":"IUBMB Life"},{"key":"66227_CR49","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1042\/bj20030478","volume":"375","author":"KM Taylor","year":"2003","unstructured":"Taylor, K. M., Morgan, H. E., Johnson, A., Hadley, L. J. & Nicholson, R. I. Structure\u2013function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters. Biochem. J. 375, 51\u201359 (2003).","journal-title":"Biochem. J."},{"key":"66227_CR50","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1271\/bbb.80910","volume":"73","author":"W Matsuura","year":"2009","unstructured":"Matsuura, W. et al. SLC39A9 (ZIP9) regulates zinc homeostasis in the secretory pathway: Characterization of the ZIP subfamily I protein in vertebrate cells. Biosci. Biotechnol. Biochem. 73, 1142\u20131148 (2009).","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"66227_CR51","doi-asserted-by":"publisher","first-page":"12802","DOI":"10.1074\/jbc.M112457200","volume":"277","author":"T Iwai","year":"2002","unstructured":"Iwai, T. et al. Molecular cloning and characterization of a novel UDP-GlcNAc:GalNAc-peptide \u03b21,3-N-Acetylglucosaminyltransferase (\u03b23Gn-T6), an enzyme synthesizing the core 3 structure of O-glycans. J. Biol. Chem. 277, 12802\u201312809 (2002).","journal-title":"J. Biol. Chem."},{"key":"66227_CR52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180242","volume":"12","author":"MS Hanes","year":"2017","unstructured":"Hanes, M. S., Moremen, K. W. & Cummings, R. D. Biochemical characterization of functional domains of the chaperone Cosmc. PLoS One 12, e0180242 (2017).","journal-title":"PLoS One"},{"key":"66227_CR53","doi-asserted-by":"publisher","first-page":"7351","DOI":"10.1073\/pnas.1015686108","volume":"108","author":"Y Qin","year":"2011","unstructured":"Qin, Y., Dittmer, P. J., Park, J. G., Jansen, K. B. & Palmer, A. E. Measuring steady-state and dynamic endoplasmic reticulum and Golgi Zn 2+ with genetically encoded sensors. Proc. Natl. Acad. Sci. U. S. A. 108, 7351\u20137356 (2011).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"66227_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08429-1","volume":"10","author":"S Watanabe","year":"2019","unstructured":"Watanabe, S. et al. Zinc regulates ERp44-dependent protein quality control in the early secretory pathway. Nat. Commun. 10, 603 (2019).","journal-title":"Nat. Commun."},{"key":"66227_CR55","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102179","volume":"18","author":"T Kambe","year":"2017","unstructured":"Kambe, T., Matsunaga, M. & Takeda, T. Understanding the contribution of zinc transporters in the function of the early secretory pathway. Int. J. Mol. Sci. 18, 2179 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"66227_CR56","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.cell.2022.02.013","volume":"185","author":"Y Yao","year":"2022","unstructured":"Yao, Y. et al. Mucus sialylation determines intestinal host-commensal homeostasis. Cell 185, 1172\u20131188 (2022).","journal-title":"Cell"},{"key":"66227_CR57","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41575-020-0331-7","volume":"17","author":"MR Kudelka","year":"2020","unstructured":"Kudelka, M. R., Stowell, S. R., Cummings, R. D. & Neish, A. S. Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD. Nat. Rev. Gastroenterol. Hepatol. 17, 597\u2013617 (2020).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"66227_CR58","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12986-019-0395-y","volume":"16","author":"Q Yu","year":"2019","unstructured":"Yu, Q. et al. The effects of zinc deficiency on homeostasis of twelve minerals and trace elements in the serum, feces, urine and liver of rats. Nutr. Metab. 16, 73 (2019).","journal-title":"Nutr. Metab."},{"key":"66227_CR59","doi-asserted-by":"publisher","first-page":"1500308","DOI":"10.1002\/admi.201500308","volume":"2","author":"T Crouzier","year":"2015","unstructured":"Crouzier, T. et al. Modulating mucin hydration and lubrication by deglycosylation and polyethylene glycol binding. Adv. Mater. Interfaces 2, 1500308 (2015).","journal-title":"Adv. Mater. Interfaces"},{"key":"66227_CR60","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1021\/acschembio.1c00689","volume":"17","author":"D Bojar","year":"2022","unstructured":"Bojar, D. et al. A useful guide to lectin binding: machine-learning directed annotation of 57 unique lectin specificities. ACS Chem. Biol. 17, 2993\u20133012 (2022).","journal-title":"ACS Chem. Biol."},{"key":"66227_CR61","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1007\/BF01536988","volume":"33","author":"JM Rhodes","year":"1988","unstructured":"Rhodes, J. M., Black, R. R. & Savage, A. Altered lectin binding by colonic epithelial glycoconjugates in ulcerative colitis and Crohn\u2019s disease. Dig. Dis. Sci. 33, 1359\u20131363 (1988).","journal-title":"Dig. Dis. Sci."},{"key":"66227_CR62","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1053\/j.gastro.2007.02.048","volume":"132","author":"P Garg","year":"2007","unstructured":"Garg, P. et al. Matrix metalloproteinase-9 regulates MUC-2 expression through its effect on goblet cell differentiation. Gastroenterology 132, 1877\u20131889 (2007).","journal-title":"Gastroenterology"},{"key":"66227_CR63","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.sbi.2012.06.005","volume":"22","author":"DR Rose","year":"2012","unstructured":"Rose, D. R. Structure, mechanism and inhibition of Golgi \u03b1-mannosidase II. Curr. Opin. Struct. Biol. 22, 558\u2013562 (2012).","journal-title":"Curr. Opin. Struct. Biol."},{"key":"66227_CR64","doi-asserted-by":"publisher","first-page":"9570","DOI":"10.1073\/pnas.0802206105","volume":"105","author":"N Shah","year":"2008","unstructured":"Shah, N., Kuntz, D. A. & Rose, D. R. Golgi \u03b1-mannosidase II cleaves two sugars sequentially in the same catalytic site. Proc. Natl. Acad. Sci. 105, 9570\u20139575 (2008).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"66227_CR65","doi-asserted-by":"publisher","first-page":"11079","DOI":"10.1074\/jbc.M116.770123","volume":"292","author":"T Taniguchi","year":"2017","unstructured":"Taniguchi, T. et al. N-Glycosylation affects the stability and barrier function of the MUC16 mucin. J. Biol. Chem. 292, 11079\u201311090 (2017).","journal-title":"J. Biol. Chem."},{"key":"66227_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2023.130412","volume":"1867","author":"Z Durin","year":"2023","unstructured":"Durin, Z., Houdou, M., Legrand, D. & Foulquier, F. Metalloglycobiology: The power of metals in regulating glycosylation. Biochim. Biophys. Acta (BBA) - Gen. Subj. 1867, 130412 (2023).","journal-title":"Biochim. Biophys. Acta (BBA) - Gen. Subj."},{"key":"66227_CR67","unstructured":"R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria (R Foundation for Statistical Computing, 2020)."},{"key":"66227_CR68","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"66227_CR69","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1093\/bioinformatics\/btm069","volume":"23","author":"W Stacklies","year":"2007","unstructured":"Stacklies, W., Redestig, H., Scholz, M., Walther, D. & Selbig, J. pcaMethods: a bioconductor package providing PCA methods for incomplete data. Bioinformatics 23, 1164\u20131167 (2007).","journal-title":"Bioinformatics"},{"key":"66227_CR70","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847\u20132849 (2016).","journal-title":"Bioinformatics"},{"key":"66227_CR71","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu, T. et al. ClusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation 2, 100141 (2021).","journal-title":"Innovation"},{"key":"66227_CR72","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","volume":"260","author":"G Grynkiewicz","year":"1985","unstructured":"Grynkiewicz, G., Poenie, M. & Tsien, R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260, 3440\u20133450 (1985).","journal-title":"J. Biol. Chem."},{"key":"66227_CR73","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods. 9, 676\u2013682 (2012).","journal-title":"Nat. Methods"},{"key":"66227_CR74","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","volume":"224","author":"S Bolte","year":"2006","unstructured":"Bolte, S. & Cordeli\u00e8res, F. P. A guided tour into subcellular colocalization analysis in light microscopy. J. Microsc. 224, 213\u2013232 (2006).","journal-title":"J. Microsc"},{"key":"66227_CR75","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1385\/0-89603-268-X:5","volume-title":"Basic Protein and Peptide Protocols","author":"JM Walker","year":"1994","unstructured":"Walker, J. M. The Bicinchoninic Acid (BCA) Assay for Protein Quantitation. In Basic Protein and Peptide Protocols Vol. vol. 32 5\u20138 (Humana Press, 1994)."},{"key":"66227_CR76","doi-asserted-by":"publisher","first-page":"207","DOI":"10.2144\/btn-2022-0012","volume":"72","author":"C Sakuma","year":"2022","unstructured":"Sakuma, C. et al. Western blotting of native proteins from agarose gels. BioTechniques 72, 207\u2013218 (2022).","journal-title":"BioTechniques"},{"key":"66227_CR77","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms6020049","volume":"6","author":"B Ringot-Destrez","year":"2018","unstructured":"Ringot-Destrez, B. et al. A sensitive and rapid method to determin the adhesion capacity of probiotics and pathogenic microorganisms to human gastrointestinal mucins. Microorganisms 6, 49 (2018).","journal-title":"Microorganisms"},{"key":"66227_CR78","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1093\/hmg\/ddw026","volume":"25","author":"S Potelle","year":"2016","unstructured":"Potelle, S. et al. Glycosylation abnormalities in Gdt1p\/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis. Hum. Mol. Genet. 25, 1489\u20131500 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"66227_CR79","doi-asserted-by":"publisher","first-page":"5242","DOI":"10.1021\/acs.analchem.3c05762","volume":"96","author":"KE Mahoney","year":"2024","unstructured":"Mahoney, K. E., Chang, V., Lucas, T. M., Maruszko, K. & Malaker, S. A. Mass spectrometry-compatible elution technique enables an improved mucin-selective enrichment strategy to probe the mucinome. Anal. Chem. 96, 5242\u20135250 (2024).","journal-title":"Anal. Chem."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-66227-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-66227-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-66227-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:04:30Z","timestamp":1786449870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-66227-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["66227"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-66227-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"assertion":[{"value":"30 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Stacy Malaker is an author on a Stanford patent related to the use of mucinases as research tools.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"24822"}}