{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T13:55:04Z","timestamp":1778162104875,"version":"3.51.4"},"reference-count":47,"publisher":"American Society for Cell Biology (ASCB)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:p>PLEKHG4B is a Cdc42-targeting guanine-nucleotide exchange factor implicated in forming epithelial cell\u2013cell junctions. Here we explored the mechanism regulating PLEKHG4B localization. PLEKHG4B localized to the basal membrane in normal Ca<jats:sup>2+<\/jats:sup>medium but accumulated at cell\u2013cell junctions upon ionomycin treatment. Ionomycin-induced junctional localization of PLEKHG4B was suppressed upon disrupting its annexin-A2 (ANXA2)-binding ability. Thus, Ca<jats:sup>2+<\/jats:sup>influx and ANXA2 binding are crucial for PLEKHG4B localization to cell\u2013cell junctions. Treatments with low Ca<jats:sup>2+<\/jats:sup>or BAPTA-AM (an intracellular Ca<jats:sup>2+<\/jats:sup>chelator) suppressed PLEKHG4B localization to the basal membrane. Mutations of the phosphoinositide-binding motif in the pleckstrin homology (PH) domain of PLEKHG4B or masking of membrane phosphatidylinositol-4,5-biphosphate [PI(4,5)P<jats:sub>2<\/jats:sub>] suppressed PLEKHG4B localization to the basal membrane, indicating that basal membrane localization of PLEKHG4B requires suitable intracellular Ca<jats:sup>2+<\/jats:sup>levels and PI(4,5)P<jats:sub>2<\/jats:sub>binding of the PH domain. Activation of mechanosensitive ion channels (MSCs) promoted PLEKHG4B localization to cell\u2013cell junctions, and their inhibition suppressed it. Moreover, similar to the PLEKHG4B knockdown phenotypes, inhibition of MSCs or treatment with BAPTA-AM disturbed the integrity of actin filaments at cell\u2013cell junctions. Taken together, our results suggest that Ca<jats:sup>2+<\/jats:sup>influx plays crucial roles in PLEKHG4B localization to cell\u2013cell junctions and the integrity of junctional actin organization, with MSCs contributing to this process.<\/jats:p>","DOI":"10.1091\/mbc.e23-05-0154","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T16:55:06Z","timestamp":1702486506000},"source":"Crossref","is-referenced-by-count":4,"title":["Calcium influx promotes PLEKHG4B localization to cell\u2013cell junctions and regulates the integrity of junctional actin filaments"],"prefix":"10.1091","volume":"35","author":[{"given":"Komaki","family":"Ninomiya","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"},{"name":"Laboratory for Histogenetic Dynamics, Graduate School of Life Sciences, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Ohta","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ukyo","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"Chiba","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanari","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erina","family":"Kuranaga","sequence":"additional","affiliation":[{"name":"Laboratory for Histogenetic Dynamics, Graduate School of Life Sciences, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"},{"name":"Laboratory for Histogenetic Dynamics, Graduate School and Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606\u20118304, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumasa","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"},{"name":"Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensaku","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"},{"name":"Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai, Miyagi 980-8578, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.03.053"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200411109"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14036259"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028746"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2106"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4161\/21541248.2014.973760"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2009.06.044"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.362"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121477"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-06-0499"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1242\/bio.058843"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/35103068"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029181"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1661"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207747200"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2927"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400821"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.67"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1247\/csf.21002"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)39780-7"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.07.155"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e17-01-0051"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.6.1155"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3136"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2328"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.051"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.097923"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028738"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nature09823"},{"key":"B31","doi-asserted-by":"crossref","first-page":"jcs.249078","DOI":"10.1242\/jcs.249078","volume":"134","author":"Ninomiya K","year":"2021","journal-title":"J Cell Sci"},{"key":"B32","first-page":"245","volume":"161","author":"Ohashi K","year":"2017","journal-title":"J Biochem"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051286"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718177115"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.02.096"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01208"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1587"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106731200"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3802"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.06.011"},{"key":"B41","first-page":"409245","author":"Tsai FC","year":"2015","journal-title":"Biomed Res Int"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002033"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202105107"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408215200"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70822-4"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo1461"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129551"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T22:12:46Z","timestamp":1730844766000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.E23-05-0154"}},"subtitle":[],"editor":[{"given":"Alpha","family":"Yap","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,1]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,1]]}},"alternative-id":["10.1091\/mbc.E23-05-0154"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e23-05-0154","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,1]]},"article-number":"ar24"}}