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Blood, 14 May 2009, Vol. 113, No. 20, pp. 5010-5018. Prepublished online as a Blood First Edition Paper on March 6, 2009; DOI 10.1182/blood-2008-09-181206. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-09-181206v1 113/20/5010    most recent Alert me when this article is cited Alert me if a correction is posted 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 Nightingale, T. D. Articles by Cutler, D. F. Search for Related Content PubMed PubMed Citation Articles by Nightingale, T. D. Articles by Cutler, D. F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 25, 2008 Accepted February 15, 2009 Rab27a and MyRIP regulate the amount and multimeric state of VWF released from endothelial cells Thomas D. Nightingale, Krupa Pattni, Alistair N. Hume, Miguel C. Seabra, and Daniel F. Cutler* MRC Laboratory of Molecular Cell Biology, Cell Biology Unit and Department of Cell and Developmental Biology, University College London, London, United Kingdom National Heart and Lung Institute, Imperial College London, London, United Kingdom * Corresponding author; email: d.cutler{at}ucl.ac.uk. Endothelial cells contain cigar-shaped secretory organelles called Weibel Palade Bodies (WPB) that play a crucial role in both hemostasis and the initiation of inflammation. The major cargo protein of WPB is von Willebrand Factor (VWF). In unstimulated cells this protein is stored in a highly multimerized state coiled into protein tubules, but following secretagogue stimulation and exocytosis it unfurls, under shear force, as long platelet-binding strings. Small GTPases of the Rab family play a key role in organelle function. Using siRNA depletion in primary endothelial cells we have identified a role for the WPB-associated Rab27a and its effector MyRIP. Both these proteins are present on only mature WPB, and this rab/effector complex appears to anchor these WPB to peripheral actin. Depletion of either the Rab or its effector results in a loss of peripheral WPB localization, and this destabilization is coupled with an increase in both basal and stimulated secretion. The VWF released from Rab27a depleted cells is less multimerized, and the VWF strings seen under flow are shorter. Our results indicate that this Rab/effector complex controls peripheral distribution and prevents release of incompletely processed WPB content. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Berriman, S. Li, L. J. Hewlett, S. Wasilewski, F. N. Kiskin, T. Carter, M. J. Hannah, and P. B. Rosenthal Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells PNAS, October 13, 2009; 106(41): 17407 - 17412. [Abstract] [Full Text] [PDF]

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