SEARCH:   Advanced

Blood, 15 December 2005, Vol. 106, No. 13, pp. 4159-4166. Prepublished online as a Blood First Edition Paper on August 25, 2005; DOI 10.1182/blood-2005-04-1356. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1356v1 106/13/4159    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 Lo, B. Articles by Kahr, W. H. A. Search for Related Content PubMed PubMed Citation Articles by Lo, B. Articles by Kahr, W. H. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Requirement of VPS33B, a member of the Sec1/Munc18 protein family, in megakaryocyte and platelet -granule biogenesis Bryan Lo, Ling Li, Paul Gissen, Hilary Christensen, Patrick J. McKiernan, Charles Ye, Mohamed Abdelhaleem, Jason A. Hayes, Michael D. Williams, David Chitayat, and Walter H. A. Kahr From the Department of Paediatrics, Division of Clinical and Metabolic Genetics, the Programme in Cell Biology, the Department of Paediatrics, Division of Haematology/Oncology, the Department of Paediatric Laboratory Medicine, and the Department of Anesthesia, The Hospital for Sick Children, University of Toronto, ON, Canada; the Section of Medical and Molecular Genetics, University of Birmingham, Birmingham Women's Hospital, Edgbaston, Birmingham, United Kingdom; The Liver Unit and the Department of Haematology, Birmingham Children's Hospital, Birmingham, United Kingdom; and the Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, ON, Canada. Bleeding problems are associated with defects in platelet -granules, yet little is known about how these granules are formed and released. Mutations affecting VPS33B, a novel Sec1/Munc18 protein, have recently been linked to arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome. We have characterized platelets from patients with ARC syndrome and observed reduced aggregation with arachidonate and adenosine diphosphate (ADP). Structural abnormalities seen in ARC platelets included increased platelet size, a pale appearance in blood films, elevated numbers of -granules, and completely absent -granules. Soluble and membrane-bound -granule proteins were significantly decreased or undetectable in ARC platelets, suggesting that both the releasable protein pools and membrane components of -granules were absent. The role of VPS33B in platelet granule biogenesis was evaluated by immunofluorescence microscopy in normal human megakaryocytes. VPS33B colocalized appreciably with markers of -granules, moderately with late endosomes/lysosomes, minimally with -granules/lysosomes, and not with cis-Golgi complexes. VPS33B protein expression determined by immunoblotting confirmed the presence of VPS33B in control fibroblasts but not in ARC fibroblasts, and in normal megakaryocytes but not in platelets. We conclude that like other Sec1/Munc18 proteins, VPS33B is involved in intracellular vesicle trafficking, being essential for the development of platelet -granules but not for granule secretion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: VPS33B: let there be -granules Robert Flaumenhaft Blood 2005 106: 4022-4023. [Full Text] [PDF] This article has been cited by other articles: C. Licht, F. G. Pluthero, L. Li, H. Christensen, S. Habbig, B. Hoppe, D. F. Geary, P. F. Zipfel, and W. H. A. Kahr Platelet-associated complement factor H in healthy persons and patients with atypical HUS Blood, November 12, 2009; 114(20): 4538 - 4545. [Abstract] [Full Text] [PDF] W. H. A. Kahr Granules and thrombus formation Blood, July 30, 2009; 114(5): 932 - 933. [Abstract] [Full Text] [PDF] H. Yang, S. Lang, Z. Zhai, L. Li, W. H. A. Kahr, P. Chen, J. Brkic, C. M. Spring, M. J. Flick, J. L. Degen, et al. Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression Blood, July 9, 2009; 114(2): 425 - 436. [Abstract] [Full Text] [PDF] G.-d. Zhu, G. Salazar, S. A. Zlatic, B. Fiza, M. M. Doucette, C. J. Heilman, A. I. Levey, V. Faundez, and S. W. L'Hernault SPE-39 Family Proteins Interact with the HOPS Complex and Function in Lysosomal Delivery Mol. Biol. Cell, February 1, 2009; 20(4): 1223 - 1240. [Abstract] [Full Text] [PDF] J. E. Italiano Jr, J. L. Richardson, S. Patel-Hett, E. Battinelli, A. Zaslavsky, S. Short, S. Ryeom, J. Folkman, and G. L. Klement Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet {alpha} granules and differentially released Blood, February 1, 2008; 111(3): 1227 - 1233. [Abstract] [Full Text] [PDF] P. Gissen and E. R Maher Cargos and genes: insights into vesicular transport from inherited human disease J. Med. Genet., September 1, 2007; 44(9): 545 - 555. [Abstract] [Full Text] [PDF] V. M. Olkkonen and E. Ikonen When intracellular logistics fails - genetic defects in membrane trafficking J. Cell Sci., December 15, 2006; 119(24): 5031 - 5045. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020