{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T20:31:38Z","timestamp":1770237098364,"version":"3.49.0"},"reference-count":58,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["1R03AR084261\u201001A1"],"award-info":[{"award-number":["1R03AR084261\u201001A1"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GMR22T1024"],"award-info":[{"award-number":["GMR22T1024"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024370","name":"Ministero dell'Istruzione e del Merito","doi-asserted-by":"publisher","award":["Dipartimenti di Eccellenza (2018\u20102022)"],"award-info":[{"award-number":["Dipartimenti di Eccellenza (2018\u20102022)"]}],"id":[{"id":"10.13039\/501100024370","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>The trimeric intracellular cation channel B (TRIC\u2010B), encoded by <jats:italic>TMEM38B<\/jats:italic>, is a potassium (K<jats:sup>+<\/jats:sup>) channel present in the endoplasmic reticulum membrane, where it counterbalances calcium (Ca<jats:sup>2+<\/jats:sup>) exit. Lack of TRIC\u2010B activity causes a recessive form of the skeletal disease osteogenesis imperfecta (OI), namely OI type XIV, characterized by impaired intracellular Ca<jats:sup>2+<\/jats:sup> flux and defects in osteoblast (OB) differentiation and activity. Taking advantage of the OB\u2010specific <jats:italic>Tmem38b<\/jats:italic> knockout mouse (<jats:italic>Runx2Cre;Tmem38b<\/jats:italic><jats:sup><jats:italic>fl<\/jats:italic>\/<jats:italic>fl<\/jats:italic><\/jats:sup>; cKO), we investigated how the ion imbalance affects the osteogenetic process. We found an abnormal cytoskeleton in the cKO OBs, with actin accumulation at OB adhesion sites. The reduced amount of active Ca<jats:sup>2+<\/jats:sup>\u2010dependent actin\u2010binding proteins myristoylated alanine\u2010rich C\u2010kinase substrate (MARCKS) and fascin, which modulate cytoskeletal actin dynamics, explains the altered cytoskeletal assembly. The actin clusters at adhesion sites trap \u03b2\u2010catenin, a key structural protein at cell\u2013cell junction sites, that abnormally accumulates despite the significant reduction in both N\u2010 and E\u2010cadherins. Besides its structural fuction at cell borders, \u03b2\u2010catenin also has a pivotal role as a transcription factor for proper osteoblastogenesis. Immunofluorescence of cKO nuclei revealed impaired nuclear \u03b2\u2010catenin translocation, further validated in human fetal OB knocked out for <jats:italic>TMEM38B<\/jats:italic>, which was not rescued by specifically stimulating the canonical Wnt pathway. Thus, we demonstrated <jats:italic>in vitro<\/jats:italic> that alterations of intracellular Ca<jats:sup>2+<\/jats:sup> homeostasis, as a consequence of lack of TRIC\u2010B, cause cytoskeleton disorganization in cKO OBs, resulting in abnormal \u03b2\u2010catenin accumulation at cell adhesion sites and reduced nuclear \u03b2\u2010catenin translocation, contributing to impaired osteoblastogenesis.<\/jats:p>","DOI":"10.1111\/febs.17399","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:57:05Z","timestamp":1737421025000},"page":"1920-1933","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lack of <scp>TRIC<\/scp>\u2010B dysregulates cytoskeleton assembly, trapping \u03b2\u2010catenin at osteoblast adhesion sites"],"prefix":"10.1111","volume":"292","author":[{"given":"Barbara Maria","family":"Contento","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Biochemistry Unit University of Pavia  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Garibaldi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Biochemistry Unit University of Pavia  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Sala","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Biochemistry Unit University of Pavia  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Palladino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Biochemistry Unit University of Pavia  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Oldani","sequence":"additional","affiliation":[{"name":"Optical Microscopy Facility, Centro Grandi Strumenti University of Pavia  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Carriero","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The City College of New York  NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Forlino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Biochemistry Unit University of Pavia  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1430-2934","authenticated-orcid":false,"given":"Roberta","family":"Besio","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Biochemistry Unit University of Pavia  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-011-0431-4"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218323"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05928"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b16-00612"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.52"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006156"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2023.06.004"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1002914"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0257254"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-023-10005-4"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.301816"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.036798"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2023.05.002"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008284"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.01.024"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-007-9159-2"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/351320a0"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology9110403"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15111369"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.11.7320-7328.1994"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1549"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-013-9530-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.150"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.437913"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317768"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.02.017"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.01.023"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601230"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0204171"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.20034"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20033"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10237-003-0029-0"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv328"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2017.08.007"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010429"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1171930"},{"key":"e_1_2_10_39_1","article-title":"Protein kinase C signaling and cell cycle regulation","volume":"3","author":"Black AR","year":"2012","journal-title":"Front Immunol"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/356618a0"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-018-0445-1"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.635783"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.110046"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.09.020"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600645R"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2012.08715.x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.183699"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03563.x"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90558-7"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90451-J"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094291"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206454200"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.42.090401.151133"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155415586961"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.1.131-139.2003"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24803"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.01.015"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169075"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2021.03.001"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.17399","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T11:01:32Z","timestamp":1753441292000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.17399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":58,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/febs.17399"],"URL":"https:\/\/doi.org\/10.1111\/febs.17399","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,20]]},"assertion":[{"value":"2024-07-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}