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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3949-3957. Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-03-1179. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1179v1 104/13/3949    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 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 Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Cytoskeleton Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Interactions between the megakaryocyte/platelet-specific 1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions Harald Schulze, Manav Korpal, Wolfgang Bergmeier, Joseph E. Italiano, Jr, Sharon M. Wahl, and Ramesh A. Shivdasani From the Dana-Farber Cancer Institute; Harvard Medical School; Center for Blood Research (CBR) Institute for Biomedical Research; and Brigham and Women's Hospital, Boston, MA; and the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD. Platelet-restricted 1 tubulin is required for optimal thrombopoiesis and discoid cell shape. To identify interacting factors, we used the divergent 1-tubulin C-terminus as the bait in a yeast 2-hybrid screen of megakaryocyte (MK) cDNAs. We isolated secretory leukocyte protease inhibitor (SLPI), a serine protease antagonist characterized principally as a secreted factor with multiple roles in inflammation. SLPI is expressed in MKs and platelets in 2 discrete compartments. One pool resides in punctate cytoplasmic structures, whereas a significant fraction localizes along peripheral microtubules (MTs) and is lost with cold-induced MT disruption or in 1 tubulin-/- platelets. These findings reveal unexpected interaction between a prominent cytoskeletal protein and an inhibitor of proteolysis. SLPI-/- mice show intact proplatelet formation, platelet numbers and shape, and marginal MT bands; thus, SLPI is not essential for thrombopoiesis. However, SLPI is released upon platelet activation, which also reverses its association with the resting marginal band. Platelet SLPI inhibits neutrophil elastase, an activity that is reduced when 1 tubulin is absent. We conclude that SLPI localizes in part along the MK and platelet MT cytoskeleton by virtue of specific interactions with 1 tubulin. SLPI may thus have unanticipated roles in MK and platelet functions, including regulated proteolysis after activation. (Blood. 2004;104:3949-3957) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Schulze, M. Dose, M. Korpal, I. Meyer, J. E. Italiano Jr., and R. A. Shivdasani RanBP10 Is a Cytoplasmic Guanine Nucleotide Exchange Factor That Modulates Noncentrosomal Microtubules J. Biol. Chem., May 16, 2008; 283(20): 14109 - 14119. [Abstract] [Full Text] [PDF] S. Patel-Hett, J. L. Richardson, H. Schulze, K. Drabek, N. A. Isaac, K. Hoffmeister, R. A. Shivdasani, J. C. Bulinski, N. Galjart, J. H. Hartwig, et al. Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules Blood, May 1, 2008; 111(9): 4605 - 4616. [Abstract] [Full Text] [PDF] H. Schulze, M. Korpal, J. Hurov, S.-W. Kim, J. Zhang, L. C. Cantley, T. Graf, and R. A. Shivdasani Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis Blood, May 15, 2006; 107(10): 3868 - 3875. [Abstract] [Full Text] [PDF] S. R. Patel, J. L. Richardson, H. Schulze, E. Kahle, N. Galjart, K. Drabek, R. A. Shivdasani, J. H. Hartwig, and J. E. Italiano Jr Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes Blood, December 15, 2005; 106(13): 4076 - 4085. [Abstract] [Full Text] [PDF]

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