{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:13:46Z","timestamp":1792167226414,"version":"4.4.0"},"reference-count":30,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,10,15]]},"abstract":"<jats:p>SEDT (spondyloepiphyseal dysplasia tarda) is a late-onset X-linked recessive skeletal dysplasia caused by mutations in the gene SEDL coding for sedlin. In the present paper, we investigated four missense mutations observed in SEDT and compare biochemical and cellular characteristics relative to the wild-type protein to address the mechanism of disease and to gain insight into the function of the sedlin protein. In situ hybridization and immunohistochemical experiments in mouse growth plates revealed sedlin to be predominantly expressed in proliferating and hypertrophic chondrocytes. Cell culture studies showed that the wild-type protein localized predominantly in the vicinity of the nucleus and the Golgi, with further localization around the cytoplasm, whereas mutation resulted in mislocalization. The D47Y mutant was expressed similarly to the wild-type, but the S73L, F83S and V130D mutants showed particularly low levels of expression that were rescued in the presence of the proteasome inhibitor MG132 (benzyloxycarbonyl-leucylleucylleucinal). Furthermore, whereas the D47Y mutant folded similarly and had similar stability to the wild-type sedlin as shown by CD and fluorescence, the S73L, F83S and V130D mutants all misfolded during expression. Two independent assays showed that the D47Y mutation resulted in an increased affinity for the transport protein particle component Bet3 compared with the wild-type sedlin. Our results suggest that the sedlin mutations S73L, F83S and V130D cause SEDT by sedlin misfolding, whereas the D47Y mutation may influence normal TRAPP (transport protein particle) dynamics.<\/jats:p>","DOI":"10.1042\/bj20090541","type":"journal-article","created":{"date-parts":[[2009,8,5]],"date-time":"2009-08-05T14:22:35Z","timestamp":1249482155000},"page":"233-242","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Biochemical consequences of sedlin mutations that cause spondyloepiphyseal dysplasia tarda"],"prefix":"10.1042","volume":"423","author":[{"given":"Mei\u00a0Y.","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb\u00a0C.\u00a0Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith\u00a0D.\u00a0K.","family":"Luk","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn\u00a0S.\u00a0E.","family":"Cheah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian\u00a0A.","family":"Tanner","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2009,9,25]]},"reference":[{"key":"2021112215153729300_B1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1302\/0301-620X.67B1.3155744","article-title":"The prevalence of skeletal dysplasias: an estimate of their minimum frequency and the number of patients requiring orthopaedic care","volume":"67","author":"Wynne-Davies","year":"1985","journal-title":"J. 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