{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:23:56Z","timestamp":1761060236634,"version":"3.37.3"},"reference-count":38,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T00:00:00Z","timestamp":1479168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007034","name":"Thales Group","doi-asserted-by":"publisher","award":["380170"],"award-info":[{"award-number":["380170"]}],"id":[{"id":"10.13039\/501100007034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009250","name":"National Institute for Social Care and Health Research","doi-asserted-by":"publisher","award":["HP\u201014\u201016"],"award-info":[{"award-number":["HP\u201014\u201016"]}],"id":[{"id":"10.13039\/100009250","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":[[2016,12]]},"abstract":"<jats:p>Hereditary leukonychia is a rare genetic nail disorder characterized by distinctive whitening of the nail plate of all 20 nails. Hereditary leukonychia may exist as an isolated feature, or in simultaneous occurrence with other cutaneous or systemic pathologies. Associations between hereditary leukonychia and mutations in the gene encoding phospholipase C delta\u20101 (<jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b41) have previously been identified. However, the molecular mechanisms underlying <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b41 mutations and hereditary leukonychia remain uncharacterized. In the present study, we introduced hereditary leukonychia\u2010linked human <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b41 mutations (C209R, A574T and S740R) into equivalent residues of rat <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b41 (C188R, A553T and S719R), and investigated their effect on the biophysical and biochemical properties of the <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b41 protein. Our data suggest that these <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b41 mutations associated with hereditary leukonychia do not uniformly alter the enzymatic ability of this protein leading to loss\/gain of function, but result in significantly divergent enzymatic properties. We demonstrate here for the first time the importance of <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u2010mediated calcium (Ca<jats:sup>2+<\/jats:sup>) signalling within the manifestation of hereditary leukonychia. <jats:styled-content style=\"fixed-case\">PLC<\/jats:styled-content>\u03b41 is almost ubiquitous in mammalian cells, which may explain why hereditary leukonychia manifests in association with other systemic pathologies relating to keratin expression.<\/jats:p>","DOI":"10.1111\/febs.13939","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T19:27:59Z","timestamp":1479324479000},"page":"4502-4514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mutations in <scp>PLC<\/scp>\u03b41 associated with hereditary leukonychia display divergent <scp>PIP<\/scp>2 hydrolytic function"],"prefix":"10.1111","volume":"283","author":[{"given":"Michail","family":"Nomikos","sequence":"first","affiliation":[{"name":"College of Medicine Qatar University Doha Qatar"},{"name":"College of Biomedical and Life Sciences School of Biosciences Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4390-4854","authenticated-orcid":false,"given":"Angelos","family":"Thanassoulas","sequence":"additional","affiliation":[{"name":"National Center for Scientific Research \u2018Demokritos\u2019 Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad","family":"Beck","sequence":"additional","affiliation":[{"name":"College of Biomedical and Life Sciences School of Dentistry Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Theodoridou","sequence":"additional","affiliation":[{"name":"College of Biomedical and Life Sciences School of Biosciences Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmine","family":"Kew","sequence":"additional","affiliation":[{"name":"College of Biomedical and Life Sciences School of Biosciences Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junaid","family":"Kashir","sequence":"additional","affiliation":[{"name":"College of Biomedical and Life Sciences School of Biosciences Cardiff University UK"},{"name":"College of Medicine Alfaisal University Riyadh Saudi Arabia"},{"name":"Department of Comparative Medicine King Faisal Specialist Hospital &amp; Research Center Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian L.","family":"Calver","sequence":"additional","affiliation":[{"name":"College of Biomedical and Life Sciences School of Biosciences Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Matthews","sequence":"additional","affiliation":[{"name":"College of Biomedical and Life Sciences School of Biosciences Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Rizkallah","sequence":"additional","affiliation":[{"name":"College of Biomedical and Life Sciences School of Medicine Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zili","family":"Sideratou","sequence":"additional","affiliation":[{"name":"National Center for Scientific Research \u2018Demokritos\u2019 Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Nounesis","sequence":"additional","affiliation":[{"name":"National Center for Scientific Research \u2018Demokritos\u2019 Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. Anthony","family":"Lai","sequence":"additional","affiliation":[{"name":"College of Biomedical and Life Sciences School of Biosciences Cardiff University UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.014"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.10962.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2012.1852"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2008.41.6.415"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183750"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/380595a0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.41.25316"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1822"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.512186"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.06.018"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21995"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.07.082"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90219-8"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi962466t"},{"key":"e_1_2_9_16_1","first-page":"65","article-title":"Fluorescence spectroscopy","volume":"40","author":"Royer CA","year":"1995","journal-title":"Methods Mol Biol"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00478-3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.083485"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gat070"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1987.tb13435.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500629200"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20101772"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.08.035"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024419"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.10.5.12726"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.92"},{"key":"e_1_2_9_27_1","first-page":"179","article-title":"Epigenetic inactivation of PLCD1 in chronic myeloid leukemia","volume":"30","author":"Song JJ","year":"2012","journal-title":"Int J Mol Med"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080233"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1500"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.08.006"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0996-788"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2004.05994.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-9239com"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2011.11.017"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560041120"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0134(19990515)35:3<307::AID-PROT4>3.0.CO;2-3"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.20853"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl327"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1993.1450"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffebs.13939","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffebs.13939","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.13939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T04:14:46Z","timestamp":1696220086000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.13939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,15]]},"references-count":38,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1111\/febs.13939"],"URL":"https:\/\/doi.org\/10.1111\/febs.13939","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"type":"print","value":"1742-464X"},{"type":"electronic","value":"1742-4658"}],"subject":[],"published":{"date-parts":[[2016,11,15]]},"assertion":[{"value":"2016-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}