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.
From: Department of Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, 816G ARC, Philadelphia, PA 19104, USA.
Blood
- Publish Date: Oct 2006
- ISSN: 0006-4971
- Volume: 108
- Issue: 7
- Pages: 2207-15
- Medium: Print
- Language: English
- Citation (JAMA): Shang Dezhi, Zheng X Wu, Niiya Masami, et al. 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.. Blood Oct 2006;108:2207-15
Abstract
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.
Mesh Headings (Keywords): ADAM Proteins, Animals, Cells, Cultured, Cholesterol, Dogs, Endothelium, Vascular, Humans, Membrane Microdomains, Microscopy, Fluorescence, Models, Biological, Plasmids, Protein Structure, Tertiary, von Willebrand Factor
Check for Full Text / PubMed Unique Identifier (PMID): 16597588
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.