{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:49:34Z","timestamp":1788871774647,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T00:00:00Z","timestamp":1424044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Donation Fund for Neurology Research (SLH)"},{"name":"Henry G Leong Professorship in Neurology (SLH)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2015,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Familial spastic paraplegia (\n FSP<\/jats:styled-content>\n ) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. Recently, we described a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium\n ATP<\/jats:styled-content>\n ase (\n PMCA<\/jats:styled-content>\n 4, or\n ATP<\/jats:styled-content>\n 2B4) gene in a Chinese family with autosomal dominant\n FSP<\/jats:styled-content>\n . Further to this finding, here we describe the functional effect of this mutation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n As\n PMCA<\/jats:styled-content>\n 4 removes cytosolic calcium, we measured transient changes and the time\u2010dependent decay of cytosolic calcium level as visualized by using\n fura\u20102<\/jats:italic>\n fluorescent dye with confocal microscopy in human\n SH<\/jats:styled-content>\n \u2010\n SY<\/jats:styled-content>\n 5Y neuroblastoma cells overexpressing either wild\u2010type or R268Q mutant\n PMCA<\/jats:styled-content>\n 4.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Overexpressing both wild\u2010type and R268Q\n PMCA<\/jats:styled-content>\n 4 significantly reduced maximum calcium surge after\n KC<\/jats:styled-content>\n l\u2010induced depolarization as compared with vector control cells. However, cells overexpressing mutant\n PMCA<\/jats:styled-content>\n 4 protein demonstrated significantly higher level of calcium surge when compared with wild\u2010type. Furthermore, the steady\u2010state cytosolic calcium concentration in these mutant cells remained markedly higher than the wild\u2010type after\n SERCA<\/jats:styled-content>\n inhibition by thapsigargin.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our result showed that p.R268Q mutation in\n PMCA<\/jats:styled-content>\n 4 resulted in functional changes in calcium homeostasis in human neuronal cells. This suggests that calcium dysregulation may be associated with the pathogenesis of\n FSP<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/brb3.321","type":"journal-article","created":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T04:33:11Z","timestamp":1424061191000},"source":"Crossref","is-referenced-by-count":32,"title":["PMCA<\/scp>\n 4 (\n ATP<\/scp>\n 2B4) mutation in familial spastic paraplegia causes delay in intracellular calcium extrusion"],"prefix":"10.1002","volume":"5","author":[{"given":"Philip Wing\u2010Lok","family":"Ho","sequence":"first","affiliation":[{"name":"Division of Neurology Department of Medicine University of Hong Kong Hong Kong China"},{"name":"Research Centre of Heart, Brain, Hormone and Healthy Aging University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley Yin\u2010Yu","family":"Pang","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaoxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Hong Kong Hong Kong China"},{"name":"Centre for Reproduction, Development and Growth University of Hong Kong Hong Kong China"},{"name":"Centre for Genomic Sciences University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zero Ho\u2010Man","family":"Tse","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Hiu\u2010Wai","family":"Kung","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pak\u2010Chung","family":"Sham","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Hong Kong Hong Kong China"},{"name":"Centre for Reproduction, Development and Growth University of Hong Kong Hong Kong China"},{"name":"Centre for Genomic Sciences University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Leong","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010neuro\u2010062111\u2010150400"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12193"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399402005392"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.38.23741"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.03.025"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.09.004"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.09.016"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3386"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-009-9109-y"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104790"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247363"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106817200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506950200"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036052"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.18433\/J3Z011"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1152\/physrev.2001.81.1.21","article-title":"Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps","volume":"8","author":"Strehler E.","year":"2001","journal-title":"Physiol. 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