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To understand how <jats:italic>Lrrk1<\/jats:italic> regulates osteoclast function by modulating cytoskeleton rearrangement, we examined the proteins that are differentially phosphorylated in wild\u2010type mice and <jats:italic>Lrrk1<\/jats:italic>\u2010deficient osteoclasts by metal affinity purification coupled liquid chromatography\/mass spectrometry (LC\/MS) analyses. One of the candidates that we identified by LC\/MS is L\u2010plastin, an actin bundling protein. We found that phosphorylation of L\u2010plastin at serine (Ser) residues 5 was present in wild\u2010type osteoclasts but not in <jats:italic>Lrrk1<\/jats:italic>\u2010deficient cells. Western blot analyses with antibodies specific for Ser5 phosphorylated L\u2010plastin confirmed the reduced L\u2010plastin Ser5 phosphorylation in <jats:italic>Lrrk1<\/jats:italic> knockout (KO) osteoclasts. micro computed tomography (Micro\u2010CT) analyses revealed that the trabecular bone volume of the distal femur was increased by 27% in the 16 to 21\u2010week\u2010old L\u2010plastin KO females as compared with the wild\u2010type control mice. The ratio of bone volume to tissue volume and connectivity density were increased by 44% and 47% (both <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05), respectively, in L\u2010plastin KO mice. Our data suggest that targeted disruption of L\u2010plastin increases trabecular bone volume, and phosphorylation of Ser5 in L\u2010plastin in the <jats:italic>Lrrk1<\/jats:italic> signaling pathway may in part contribute to actin assembly in mature osteoclasts.<\/jats:p>","DOI":"10.1002\/jcb.27377","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T06:54:55Z","timestamp":1535007295000},"page":"10351-10357","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>LRRK1<\/i> regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L\u2010plastin"],"prefix":"10.1002","volume":"119","author":[{"given":"Mingjue","family":"Si","sequence":"first","affiliation":[{"name":"Department of Radiology Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China"},{"name":"Department of Medicine Loma Linda University Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Goodluck","sequence":"additional","affiliation":[{"name":"Musculoskeletal Disease Center Jerry L. Pettis Memorial VA Medical Center Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canjun","family":"Zeng","sequence":"additional","affiliation":[{"name":"Musculoskeletal Disease Center Jerry L. Pettis Memorial VA Medical Center Loma Linda California"},{"name":"Department of Orthopedics The Third Affiliated Hospital of Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songqin","family":"Pan","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility University of California Riverside California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Todd","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon Celeste","family":"Morley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine St. Louis Missouri"},{"name":"Department of Pathology and Immunology Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhong","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Medicine Loma Linda University Loma Linda California"},{"name":"Musculoskeletal Disease Center Jerry L. Pettis Memorial VA Medical Center Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subburaman","family":"Mohan","sequence":"additional","affiliation":[{"name":"Department of Medicine Loma Linda University Loma Linda California"},{"name":"Musculoskeletal Disease Center Jerry L. Pettis Memorial VA Medical Center Loma Linda California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3984-2427","authenticated-orcid":false,"given":"Weirong","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Medicine Loma Linda University Loma Linda California"},{"name":"Musculoskeletal Disease Center Jerry L. Pettis Memorial VA Medical Center Loma Linda California"},{"name":"Department of Orthopedics The Third Affiliated Hospital of Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,22]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119668"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21464"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.14219\/jada.archive.2006.0350"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjoms.2009.08.030"},{"key":"e_1_2_6_1_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1010650"},{"key":"e_1_2_6_1_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.1360"},{"key":"e_1_2_6_1_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-011-0085-9"},{"key":"e_1_2_6_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1695"},{"key":"e_1_2_6_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1935"},{"key":"e_1_2_6_1_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103756"},{"key":"e_1_2_6_1_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00189.2016"},{"key":"e_1_2_6_1_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2017.3"},{"key":"e_1_2_6_1_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903851"},{"key":"e_1_2_6_1_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00229.2010"},{"key":"e_1_2_6_1_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00610-09"},{"key":"e_1_2_6_1_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.099697"},{"key":"e_1_2_6_1_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02874"},{"key":"e_1_2_6_1_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1998.17.1041"},{"key":"e_1_2_6_1_20_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-276311"},{"key":"e_1_2_6_1_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.16.9331"},{"key":"e_1_2_6_1_22_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031114"},{"key":"e_1_2_6_1_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001868"},{"key":"e_1_2_6_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2012.07.004"},{"key":"e_1_2_6_1_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8905"},{"key":"e_1_2_6_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90499-O"},{"key":"e_1_2_6_1_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.086280"},{"key":"e_1_2_6_1_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2733"},{"key":"e_1_2_6_1_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636320"},{"key":"e_1_2_6_1_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041366"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.27377","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.27377","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.27377","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.27377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T16:14:07Z","timestamp":1744820047000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.27377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,22]]},"references-count":29,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1002\/jcb.27377"],"URL":"https:\/\/doi.org\/10.1002\/jcb.27377","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,22]]},"assertion":[{"value":"2018-03-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}