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Shaping of terminal megakaryocyte differentiation and proplatelet development by sphingosine-1-phosphate receptor S1P4.
FASEB J. 24, 4701-4710 (2010)
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
Keywords
Platelets; Lysophospholipids; Receptor-deficient mice
Language
english
Publication Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
0892-6638
e-ISSN
1530-6860
Journal
FASEB Journal
Quellenangaben
Volume: 24,
Issue: 12,
Pages: 4701-4710
Publisher
Wiley
Publishing Place
Bethesda, Md.
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)
PSP Element(s)
G-501700-003
PubMed ID
20686109
Scopus ID
78649740029
Erfassungsdatum
2010-12-13