{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,17]],"date-time":"2022-04-17T10:10:11Z","timestamp":1650190211561},"reference-count":34,"publisher":"Georg Thieme Verlag KG","issue":"12","funder":[{"name":"MURST grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Cysteines play a key part in von Willebrand factor (VWF) dimerisation and polymerisation, and their loss may severely affect VWF structure and function. We report on three patients with type 3 von Willebrand disease carrying the new c.1751G&gt;T missense mutation that induces the substitution of cysteine 584 by phenylalanine (C584F), and the deletion of seven nucleotides in exon 7 (c.729_735del), producing a premature stop codon at position 454 (E244Lfs*211). VWF was almost undetectable in the patients\u2019 plasma and platelets, while a single, poorly represented, oligomer emerged on plasma VWF multimer analysis. No post-DDAVP increase in VWF and factor VIII was observed. Expressing human recombinant C584F-VWF in HEK293T cells showed that C584F-VWF was synthesised and multimerised but not secreted \u2013 apart from the first oligomer, which was slightly represented in the conditioned medium, with a pattern similar to the patients\u2019 plasma VWF. The in vitro expression of the E244Lfs*211\u2013VWF revealed a defective synthesis of the mutated VWF, with a behavior typical of loss of function mutations. Cellular trafficking, investigated in HEK293 cells, indicated a normal C584F-VWF content in the endoplasmic reticulum and Golgi apparatus, confirming the synthesis and multimerisation of C584F-VWF. No pseudo-Weibel Palade bodies were demonstrable, however, suggesting that C584F mutation impairs the storage of C584F-VWF. These findings point to cysteine 584 having a role in the release of VWF and its targeting to pseudo-Weibel Palade bodies in vitro, as well as in its storage and release by endothelial cells in vivo.<\/jats:p>","DOI":"10.1160\/th14-04-0391","type":"journal-article","created":{"date-parts":[[2014,9,18]],"date-time":"2014-09-18T08:23:14Z","timestamp":1411028594000},"page":"1159-1166","source":"Crossref","is-referenced-by-count":2,"title":["Loss of cysteine 584 impairs the storage and release, but not the synthesis of von Willebrand factor"],"prefix":"10.1160","volume":"112","author":[{"given":"Viviana","family":"Daidone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Barbon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Pontara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grazia","family":"Cattini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Gallinaro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Zampese","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Pizzo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Casonato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2017,11,18]]},"reference":[{"key":"10.1160\/TH14-04-0391-1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.395"},{"key":"10.1160\/TH14-04-0391-2","doi-asserted-by":"publisher","DOI":"10.1053\/beha.2001.0133"},{"key":"10.1160\/TH14-04-0391-3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02146.x"},{"key":"10.1160\/TH14-04-0391-4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.5.1906"},{"key":"10.1160\/TH14-04-0391-5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108846"},{"key":"10.1160\/TH14-04-0391-6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.06.110190.001245"},{"key":"10.1160\/TH14-04-0391-7","first-page":"2123","volume":"99","author":"Wagner","year":"1984","journal-title":"J Biol Chem"},{"key":"10.1160\/TH14-04-0391-8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1182\/blood.V69.1.27.27","volume":"69","author":"Wagner","year":"1987","journal-title":"Blood"},{"key":"10.1160\/TH14-04-0391-9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.7.1955"},{"key":"10.1160\/TH14-04-0391-10","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.23.1.101"},{"key":"10.1160\/TH14-04-0391-11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03375.x"},{"key":"10.1160\/TH14-04-0391-12","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.007781"},{"key":"10.1160\/TH14-04-0391-13","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.99.6.2123"},{"key":"10.1160\/TH14-04-0391-14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-442285"},{"key":"10.1160\/TH14-04-0391-15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-05-1401"},{"key":"10.1160\/TH14-04-0391-16","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1182\/blood.V74.6.2028.2028","volume":"74","author":"Casonato","year":"1989","journal-title":"Blood"},{"key":"10.1160\/TH14-04-0391-17","doi-asserted-by":"publisher","DOI":"10.1097\/00001721-199204000-00003"},{"key":"10.1160\/TH14-04-0391-18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1970.tb01615.x"},{"key":"10.1160\/TH14-04-0391-19","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(97)90147-5"},{"key":"10.1160\/TH14-04-0391-20","doi-asserted-by":"crossref","first-page":"19514","DOI":"10.1016\/S0021-9258(19)47144-5","volume":"264","author":"Mancuso","year":"1989","journal-title":"J Biol Chem"},{"key":"10.1160\/TH14-04-0391-21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100735108"},{"key":"10.1160\/TH14-04-0391-22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1993.tb03313.x"},{"key":"10.1160\/TH14-04-0391-23","unstructured":"Rasband, WS., ImageJ, U.\u2009S. 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