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DOI	10.1073/pnas.2019149118
	Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice
	Gonzalez-Perez V.; Martinez-Espinosa P.L.; Sala-Rabanal M.; Bharadwaj N.; Xia X.-M.; Chen A.C.; Alvarado D.; Gustafsson J.K.; Hu H.; Ciorba M.A.; Lingle C.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Goblet cells (GCs) are specialized cells of the intestinal epithelium contributing critically to mucosal homeostasis. One of the functions of GCs is to produce and secrete MUC2, the mucin that forms the scaffold of the intestinal mucus layer coating the epithelium and separates the luminal pathogens and commensal microbiota from the host tissues. Although a variety of ion channels and transporters are thought to impact on MUC2 secretion, the specific cellular mechanisms that regulate GC function remain incompletely understood. Previously, we demonstrated that leucine-rich repeat-containing protein 26 (LRRC26), a known regulatory subunit of the Ca2+-and voltage-activated K+ channel (BK channel), localizes specifically to secretory cells within the intestinal tract. Here, utilizing a mouse model in which MUC2 is fluorescently tagged, thereby allowing visualization of single GCs in intact colonic crypts, we show that murine colonic GCs have functional LRRC26-associated BK channels. In the absence of LRRC26, BK channels are present in GCs, but are not activated at physiological conditions. In contrast, all tested MUC2− cells completely lacked BK channels. Moreover, LRRC26-associated BK channels underlie the BK channel contribution to the resting transepithelial current across mouse distal colonic mucosa. Genetic ablation of either LRRC26 or BK pore-forming α-subunit in mice results in a dramatically enhanced susceptibility to colitis induced by dextran sodium sulfate. These results demonstrate that normal potassium flux through LRRC26-associated BK channels in GCs has protective effects against colitis in mice. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	LRRC26 \| Ca2+-activated K+ channels \| epithelial cells \| DSS-induced colitis \| inflammatory bowel disease
语种	英语
scopus关键词	calcium channel; calcium ion; leucine rich repeat containing protein 26; membrane protein; mucin 2; potassium channel; unclassified drug; animal cell; animal experiment; animal model; animal tissue; Article; cell function; colitis; colon mucosa; controlled study; disease course; disease predisposition; epithelium cell; goblet cell; mouse; nonhuman; priority journal; protein secretion
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180951
作者单位	Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States; McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States; Department of Internal Medicine, Division of Gastroenterology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States; Department of Medical Chemistry and Cell Biology, University of Gothenburg, Gothenburg, 405 30, Sweden; Department of Physiology, University of Gothenburg, Gothenburg, 405 30, Sweden
推荐引用方式 GB/T 7714	Gonzalez-Perez V.,Martinez-Espinosa P.L.,Sala-Rabanal M.,et al. Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice[J],2021,118(3).
APA	Gonzalez-Perez V..,Martinez-Espinosa P.L..,Sala-Rabanal M..,Bharadwaj N..,Xia X.-M..,...&Lingle C.J..(2021).Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Gonzalez-Perez V.,et al."Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).