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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2207-2215. Prepublished online as a Blood First Edition Paper on April 4, 2006; DOI 10.1182/blood-2006-02-002139. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-02-002139v1 108/7/2207    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shang, D. Articles by Zheng, X. L. Search for Related Content PubMed PubMed Citation Articles by Shang, D. Articles by Zheng, X. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine kidney cells depends on the CUB domains and their association with lipid rafts Dezhi Shang, X. Wu Zheng, Masami Niiya, and X. Long Zheng From the Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA; and The University of Pennsylvania School of Medicine, Philadelphia, PA. ADAMTS13 biosynthesis appeared to occur mainly in hepatic stellate cells, but detection of ADAMTS13 mRNA in many other tissues suggests that vascular endothelium may also produce ADAMTS13. We showed that ADAMTS13 mRNA and protein were detectable in human umbilical vein endothelial cells, aortic endothelial cells, and endothelium-derived cell line (ECV304). ADAMTS13 in cell lysate or serum-free conditioned medium cleaved von Willebrand factor (VWF) specifically. ADAMTS13 and VWF were localized to the distinct compartments of endothelial cells. Moreover, ADAMTS13 was preferentially sorted into apical domain of ECV304 and Madin-Darby canine kidney (MDCK) cells. Apical sorting of ADAMTS13 depended on the CUB domains and their association with lipid rafts. A mutation in the second CUB domain of ADAMTS13 (4143-4144insA), naturally occurring in patients with inherited thrombotic thrombocytopenic purpura, resulted in a significant reduction of ADAMTS13 secretion and a reversal of its polarity in MDCK cells. These data demonstrated that ADAMTS13 is synthesized and secreted from endothelial cells; the apically secreted ADAMTS13 from endothelial cells may contribute significantly to plasma ADAMTS13 proteases. The data also suggest a critical role of the CUB domains and a novel cargo-selective mechanism for apical sorting of a soluble ADAMTS protease in polarized cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: ADAMTS13 cleavage of ULVWF: put the action where it is needed Jing-fei Dong Blood 2006 108: 2138-2139. [Full Text] [PDF] This article has been cited by other articles: P. Zhang, W. Pan, A. H. Rux, B. S. Sachais, and X. L. Zheng The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow Blood, September 15, 2007; 110(6): 1887 - 1894. [Abstract] [Full Text] [PDF] W. Zhou, E. E. Bouhassira, and H.-M. Tsai An IAP retrotransposon in the mouse ADAMTS13 gene creates ADAMTS13 variant proteins that are less effective in cleaving von Willebrand factor multimers Blood, August 1, 2007; 110(3): 886 - 893. [Abstract] [Full Text] [PDF]

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