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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3868-3875. Prepublished online as a Blood First Edition Paper on January 24, 2006; DOI 10.1182/blood-2005-07-2755. This Article Full Text (PDF) Supplemental Figure and Video All Versions of this Article: 2005-07-2755v1 107/10/3868    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 Schulze, H. Articles by Shivdasani, R. A Search for Related Content PubMed PubMed Citation Articles by Schulze, H. Articles by Shivdasani, R. A Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 12, 2005 Accepted January 12, 2006 Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis Harald Schulze, Manav Korpal, Jonathan Hurov, Sang-We Kim, Jinghang Zhang, Lewis C Cantley, Thomas Graf, and Ramesh A Shivdasani* Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA Department of Medicine, Harvard Medical School, Boston, MA, USA; Beth Israel-Deaconess Medical Center, Boston, MA, USA Albert Einstein College of Medicine, New York, NY, USA * Corresponding author; email: ramesh_shivdasani{at}dfci.harvard.edu. To produce blood platelets, megakaryocytes elaborate proplatelets, accompanied by expansion of membrane surface area and dramatic cytoskeletal rearrangements. The invaginated demarcation membrane system (DMS), a hallmark of mature cells, has been proposed as the source of proplatelet membranes. By direct visualization of labeled DMS, here we demonstrate that this is indeed the case. Late in megakaryocyte ontogeny, the DMS gets loaded with PI-4,5-P2, a phospholipid that is confined to plasma membranes in other cells. Appearance of PI-4,5-P2 in the DMS occurs in proximity to PI-5-P-4-kinase (PIP4K), and short hairpin (sh) RNA-mediated loss of PIP4K impairs both DMS development and expansion of megakaryocyte size. Thus, PI-4,5-P2 is a marker and possibly essential component of internal membranes. PI-4,5-P2 is known to promote actin polymerization by activating Rho-like GTPases and Wiskott-Aldrich Syndrome (WASp) family proteins. Indeed, PI-4,5-P2 in the megakaryocyte DMS associates with filamentous actin. Expression of a dominant-negative N-WASp fragment or pharmacologic inhibition of actin polymerization cause similar arrests in proplatelet formation, acting at a step beyond expansion of the DMS and cell mass. These observations collectively suggest a signaling pathway wherein PI-4,5-P2 might facilitate DMS development and local assembly of actin fibers in preparation for platelet biogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Proplatelet formation: unraveling the megakaryocyte swan song Andrew D. Leavitt Blood 2006 107: 3816-3817. [Full Text] [PDF] This article has been cited by other articles: L. Gilles, D. Bluteau, S. Boukour, Y. Chang, Y. Zhang, T. Robert, P. Dessen, N. Debili, O. A. Bernard, W. Vainchenker, et al. 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Nakauchi The WAVE2/Abi1 complex differentially regulates megakaryocyte development and spreading: implications for platelet biogenesis and spreading machinery Blood, November 15, 2007; 110(10): 3637 - 3647. [Abstract] [Full Text] [PDF] B. T. Kile, A. D. Panopoulos, R. A. Stirzaker, D. F. Hacking, L. H. Tahtamouni, T. A. Willson, L. A. Mielke, K. J. Henley, J.-G. Zhang, I. P. Wicks, et al. Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia Blood, October 1, 2007; 110(7): 2371 - 2380. [Abstract] [Full Text] [PDF] T. Junt, H. Schulze, Z. Chen, S. Massberg, T. Goerge, A. Krueger, D. D. Wagner, T. Graf, J. E. Italiano Jr., R. A. Shivdasani, et al. Dynamic Visualization of Thrombopoiesis Within Bone Marrow Science, September 21, 2007; 317(5845): 1767 - 1770. [Abstract] [Full Text] [PDF] Z. Chen, O. Naveiras, A. Balduini, A. Mammoto, M. A. Conti, R. S. Adelstein, D. Ingber, G. Q. Daley, and R. A. Shivdasani The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway Blood, July 1, 2007; 110(1): 171 - 179. [Abstract] [Full Text] [PDF] Y. Chang, F. Aurade, F. Larbret, Y. Zhang, J.-P. Le Couedic, L. Momeux, J. Larghero, J. Bertoglio, F. Louache, E. Cramer, et al. Proplatelet formation is regulated by the Rho/ROCK pathway Blood, May 15, 2007; 109(10): 4229 - 4236. [Abstract] [Full Text] [PDF] Z. Chen, M. Hu, and R. A. Shivdasani Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2 Blood, February 15, 2007; 109(4): 1451 - 1459. [Abstract] [Full Text] [PDF]

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