{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:03:32Z","timestamp":1785855812941,"version":"3.56.0"},"reference-count":75,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM\u2010081748"],"award-info":[{"award-number":["GM\u2010081748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Large conductance K<jats:sup>+<\/jats:sup> channels, termed BK channels, regulate a variety of cellular and physiological functions. Although universally activated by changes in voltage or [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, the threshold for BK channel activation varies among loci of expression, often arising from cell\u2010specific regulatory subunits including a family of leucine rich repeat\u2010containing (LRRC) \u03b3 subunits (LRRC26, LRRC52, LRRC55 and LRRC38). The \u2018founding\u2019 member of this family, LRRC26, was originally identified as a tumour suppressor in various cancers. An LRRC26 knockout (KO) mouse model recently revealed that LRRC26 is also highly expressed in secretory epithelial cells and partners with BK channels in the salivary gland and colonic goblet cells to promote sustained K<jats:sup>+<\/jats:sup> fluxes likely essential for normal secretory function. To accomplish this, LRRC26 negatively shifts the range of BK channel activation such that channels contribute to K<jats:sup>+<\/jats:sup> flux near typical epithelial cell resting conditions. In colon, the absence of LRRC26 increases vulnerability to colitis. LRRC26\u2010containing BK channels are also likely important regulators of epithelial function in other loci, including airways, female reproductive tract and mammary gland. Based on an LRRC52 KO mouse model, LRRC52 regulation of large conductance K<jats:sup>+<\/jats:sup> channels plays a role both in sperm function and in cochlear inner hair cells. Although our understanding of LRRC\u2010containing BK channels remains rudimentary, KO mouse models may help define other organs in which LRRC\u2010containing channels support normal function. A key topic for future work concerns identification of endogenous mechanisms, whether post\u2010translational or via gene regulation, that may impact LRRC\u2010dependent pathologies.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp14947-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp281952","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T03:19:55Z","timestamp":1641871195000},"page":"1357-1371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The LRRC family of BK channel regulatory subunits: potential roles in health and disease"],"prefix":"10.1113","volume":"600","author":[{"given":"Vivian","family":"Gonzalez\u2010Perez","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Washington University School of Medicine  St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-6140","authenticated-orcid":false,"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Washington University School of Medicine  St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Ciorba","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Gastroenterology Washington University School of Medicine  St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9916-3795","authenticated-orcid":false,"given":"Christopher J.","family":"Lingle","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Washington University School of Medicine  St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.075234"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201912457"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf7419"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210036"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7687074"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.537bm.x"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2018.04.008"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2014.01.005"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020101406"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020101407"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2016.04.001"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.3.411"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-8-320"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-018-2151-y"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1916715117"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2021_459"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601296103"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.303407"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-005-0830-z"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1804560115"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034038"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2019149118"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1322123111"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9341"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42240"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120562"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192373"},{"key":"e_1_2_2_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_2_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-258"},{"key":"e_1_2_2_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(01)00266-4"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2016.1213930"},{"key":"e_1_2_2_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2018-000285"},{"key":"e_1_2_2_34_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2013.0108"},{"key":"e_1_2_2_35_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201511356"},{"key":"e_1_2_2_36_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201511551"},{"key":"e_1_2_2_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2016.03.015"},{"key":"e_1_2_2_38_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020010071"},{"key":"e_1_2_2_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1907065116"},{"key":"e_1_2_2_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-304695"},{"key":"e_1_2_2_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.355"},{"key":"e_1_2_2_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.38.2.243"},{"key":"e_1_2_2_43_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274524"},{"key":"e_1_2_2_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.670885"},{"key":"e_1_2_2_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00247.2013"},{"key":"e_1_2_2_46_1","first-page":"1539","article-title":"Frequent downregulation of LRRC26 by epigenetic alterations is involved in the malignant progression of triple\u2010negative breast cancer","volume":"52","author":"Miyagawa Y","year":"2018","journal-title":"Int J Oncol"},{"key":"e_1_2_2_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00511.2007"},{"key":"e_1_2_2_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702018104"},{"key":"e_1_2_2_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000093107"},{"key":"e_1_2_2_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00331.2019"},{"key":"e_1_2_2_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb1590"},{"key":"e_1_2_2_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041664"},{"key":"e_1_2_2_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00191.2006"},{"key":"e_1_2_2_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3608"},{"key":"e_1_2_2_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2016"},{"key":"e_1_2_2_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1992"},{"key":"e_1_2_2_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcp159"},{"key":"e_1_2_2_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2159"},{"key":"e_1_2_2_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00099.2012"},{"key":"e_1_2_2_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.6.3509"},{"key":"e_1_2_2_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2016.02.012"},{"key":"e_1_2_2_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2020.1746507"},{"key":"e_1_2_2_63_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51409"},{"key":"e_1_2_2_64_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.094680"},{"key":"e_1_2_2_65_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01550.2002"},{"key":"e_1_2_2_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09162"},{"key":"e_1_2_2_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205435109"},{"key":"e_1_2_2_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703081114"},{"key":"e_1_2_2_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111104108"},{"key":"e_1_2_2_70_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41129"},{"key":"e_1_2_2_71_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505302200"},{"key":"e_1_2_2_72_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100240108"},{"key":"e_1_2_2_73_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1423869112"},{"key":"e_1_2_2_74_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00401"},{"key":"e_1_2_2_75_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200609552"},{"key":"e_1_2_2_76_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0191749","article-title":"+mRNA expression of LRRC55 protein (leucine\u2010rich repeat\u2010containing protein 55) in the adult mouse brain","volume":"13","author":"Zhang YY","year":"2018","journal-title":"PLoS One"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP281952","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP281952","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP281952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T07:55:42Z","timestamp":1692863742000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP281952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":75,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1113\/JP281952"],"URL":"https:\/\/doi.org\/10.1113\/jp281952","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,24]]},"assertion":[{"value":"2021-10-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}