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pubmed-article:14975753pubmed:abstractTextThe aim of this work was to investigate sorting mechanisms of von Willebrand factor (VWF) when expressed in haematopoietic cells. The processing and sorting of both the wild-type VWF and a multimerization defective propeptide-mutant (VWF(m)) were investigated after expression in the 32D cell line. Normal proteolytic processing was observed for both proteins, however the processing of VWF(m) was much slower and a large portion was unprocessed. Results from subcellular fractionation and immunoelectron microscopy confirmed that a part of VWF, but not VWF(m), was targeted to lysosome-related granules. Partial constitutive secretion was also observed for all forms of VWF and VWF(m). Inhibition of acidification by chloroquine blocked VWF processing but allowed unprocessed pro-VWF targeting to dense organelles. In conclusion, our observations are consistent with VWF multimerization being of importance in cellular retention and targeting to lysosome-related organelles in haematopoietic cells, suggesting a role of protein aggregation for sorting in these cells.lld:pubmed
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pubmed-article:14975753pubmed:authorpubmed-author:HolmbergLarsLlld:pubmed
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pubmed-article:14975753pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:14975753pubmed:year2004lld:pubmed
pubmed-article:14975753pubmed:articleTitleSorting of Von Willebrand factor to lysosome-related granules of haematopoietic cells.lld:pubmed
pubmed-article:14975753pubmed:affiliationDepartment of Hematology, C14, BMC, S-221 84 Lund, Sweden.lld:pubmed
pubmed-article:14975753pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:14975753pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed