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Golfier, S.* ; Kondo, S.* ; Schulze, T.* ; Takeuchi, T.* ; Vassileva, G.* ; Achtman, A.H.* ; Gräler, M.H.* ; Abbondanzo, S.J.* ; Wiekowski, M.* ; Kremmer, E. ; Endo, Y.* ; Lira, S.A.* ; Bacon, K.B.* ; Lipp, M.*

Shaping of terminal megakaryocyte differentiation and proplatelet development by sphingosine-1-phosphate receptor S1P4.

FASEB J. 24, 4701-4710 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Megakaryocytes, which mature from hematopoietic progenitors in the bone marrow, further differentiate by reorganizing their cytoplasm into long proplatelet extensions that release platelets into the circulation. The molecular mechanisms underlying this highly dynamic cytoplasmic and cytoskeletal remodeling process are only poorly understood. Here we report that sphingosine 1-phosphate receptor 4 (S1P(4)) is specifically up-regulated during the development of human megakaryocytes from progenitor cells and is expressed in mature murine megakaryocytes. Megakaryocytes generated from S1P(4)-deficient murine bone marrow showed atypical and reduced formation of proplatelets in vitro. The recovery of platelet numbers after experimental thrombocytopenia was significantly delayed in S1p4(-/-) mice. Remarkably, overexpression and stimulation of S1P(4) in human erythroleukemia HEL cells promoted endomitosis, formation of cytoplasmic extensions, and subsequent release of platelet-like particles. These observations indicate that S1P(4) is involved in shaping the terminal differentiation of megakaryocytes.-Golfier, S., Kondo, S., Schulze, T., Takeuchi, T., Vassileva, G., Achtman, A. H., Gräler, M. H., Abbondanzo, S. J., Wiekowski, M., Kremmer, E., Endo, Y., Lira, S. A., Bacon, K. B., Lipp, M. Shaping of terminal megakaryocyte differentiation and proplatelet development by sphingosine-1-phosphate receptor S1P(4).
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Platelets; Lysophospholipids; Receptor-deficient mice
ISSN (print) / ISBN 0892-6638
e-ISSN 1530-6860
Journal FASEB Journal
Quellenangaben Volume: 24, Issue: 12, Pages: 4701-4710 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Bethesda, Md.
Non-patent literature Publications
Reviewing status Peer reviewed