{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:51:44Z","timestamp":1791348704385,"version":"4.3.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2015,2,13]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the subendothelial spaces and shuttles it to the capillary lumen.\n              <jats:italic>GPIHBP1<\/jats:italic>\n              missense mutations that interfere with LPL binding cause familial chylomicronemia.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              We sought to understand mechanisms by which\n              <jats:italic>GPIHBP1<\/jats:italic>\n              mutations prevent LPL binding and lead to chylomicronemia.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              We expressed mutant forms of GPIHBP1 in Chinese hamster ovary cells, rat and human endothelial cells, and\n              <jats:italic>Drosophila<\/jats:italic>\n              S2 cells. In each expression system, mutation of cysteines in GPIHBP1\u2019s Ly6 domain (including mutants identified in patients with chylomicronemia) led to the formation of disulfide-linked dimers and multimers. GPIHBP1 dimerization\/multimerization was not unique to cysteine mutations; mutations in other amino acid residues, including several associated with chylomicronemia, also led to protein dimerization\/multimerization. The loss of GPIHBP1 monomers is relevant to the pathogenesis of chylomicronemia because only GPIHBP1 monomers\u2014and not dimers or multimers\u2014are capable of binding LPL. One GPIHBP1 mutant, GPIHBP1-W109S, had distinctive properties. GPIHBP1-W109S lacked the ability to bind LPL but had a reduced propensity for forming dimers or multimers, suggesting that W109 might play a more direct role in binding LPL. In support of that idea, replacing W109 with any of 8 other amino acids abolished LPL binding\u2014and often did so without promoting the formation of dimers and multimers.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Many amino acid substitutions in GPIHBP1\u2019s Ly6 domain that abolish LPL binding lead to protein dimerization\/multimerization. Dimerization\/multimerization is relevant to disease pathogenesis, given that only GPIHBP1 monomers are capable of binding LPL.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.305085","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T06:57:39Z","timestamp":1415775459000},"page":"624-632","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["<i>GPIHBP1<\/i>\n            Missense Mutations Often Cause Multimerization of GPIHBP1 and Thereby Prevent Lipoprotein Lipase Binding"],"prefix":"10.1161","volume":"116","author":[{"given":"Anne P.","family":"Beigneux","sequence":"first","affiliation":[{"name":"From the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (A.P.B., L.G.F., S.G.Y.); Division of Nutritional Science, Cornell University, Ithaca, NY (A.B.); Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City (B.S.J.D.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (M.O.); Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (H.G., M.P.); and Molecular Biology Institute (S.G.Y.), Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren G.","family":"Fong","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (A.P.B., L.G.F., S.G.Y.); Division of Nutritional Science, Cornell University, Ithaca, NY (A.B.); Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City (B.S.J.D.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (M.O.); Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (H.G., M.P.); and Molecular Biology Institute (S.G.Y.), Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Bensadoun","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (A.P.B., L.G.F., S.G.Y.); Division of Nutritional Science, Cornell University, Ithaca, NY (A.B.); Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City (B.S.J.D.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (M.O.); Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (H.G., M.P.); and Molecular Biology Institute (S.G.Y.), Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon S.J.","family":"Davies","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (A.P.B., L.G.F., S.G.Y.); Division of Nutritional Science, Cornell University, Ithaca, NY (A.B.); Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City (B.S.J.D.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (M.O.); Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (H.G., M.P.); and Molecular Biology Institute (S.G.Y.), Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Oberer","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (A.P.B., L.G.F., S.G.Y.); Division of Nutritional Science, Cornell University, Ithaca, NY (A.B.); Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City (B.S.J.D.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (M.O.); Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (H.G., M.P.); and Molecular Biology Institute (S.G.Y.), Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"G\u00e5rdsvoll","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (A.P.B., L.G.F., S.G.Y.); Division of Nutritional Science, Cornell University, Ithaca, NY (A.B.); Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City (B.S.J.D.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (M.O.); Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (H.G., M.P.); and Molecular Biology Institute (S.G.Y.), Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ploug","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (A.P.B., L.G.F., S.G.Y.); Division of Nutritional Science, Cornell University, Ithaca, NY (A.B.); Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City (B.S.J.D.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (M.O.); Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (H.G., M.P.); and Molecular Biology Institute (S.G.Y.), Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G.","family":"Young","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (A.P.B., L.G.F., S.G.Y.); Division of Nutritional Science, Cornell University, Ithaca, NY (A.B.); Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City (B.S.J.D.); Institute of Molecular Biosciences, University of Graz, Graz, Austria (M.O.); Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark (H.G., M.P.); and Molecular Biology Institute (S.G.Y.), Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.02.002"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.04.016"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.186577"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.109.908905"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M002717"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1444"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2011.02361.x"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9406-5"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.558528"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.241406"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0300177"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.062242606"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.19"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-003-2461-2"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802579200"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.046391"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.242024"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2012.02516.x"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2006.11.013"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.2"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.189100"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.093492"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1369\/0022155413501879"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.12.058"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)40768-0"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108128200"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.1843"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10085"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0134(20010501)43:2<89::AID-PROT1021>3.0.CO;2-H"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e3281527914"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/3.8.667"},{"key":"e_1_3_5_33_2","first-page":"507","article-title":"New monoclonal antibodies in CD59: use for the analysis of peripheral blood cells from paroxysmal nocturnal haemoglobinuria (PNH) patients and for the quantitation of CD59 on normal and decay accelerating factor (DAF)-deficient erythrocytes.","volume":"75","author":"Fletcher A","year":"1992","unstructured":"Fletcher A, Bryant JA, Gardner B, Judson PA, Spring FA, Parsons SF, Mallinson G, Anstee DJ. 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