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Shaping of terminal megakaryocyte differentiation and proplatelet development by sphingosine‐1‐phosphate receptor S1P 4
Author(s) -
Golfier Sven,
Kondo Shinichi,
Schulze Tobias,
Takeuchi Tomomi,
Vassileva Galya,
Achtman Ariel H.,
Gräler Markus H.,
Abbondanzo Susan J.,
Wiekowski Maria,
Kremmer Elisabeth,
Endo Yasuhisa,
Lira Sergio A.,
Bacon Kevin B.,
Lipp Martin
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09.141473
Subject(s) - megakaryocyte , microbiology and biotechnology , thrombopoiesis , sphingosine 1 phosphate , haematopoiesis , cytoplasm , sphingosine 1 phosphate receptor , sphingosine , platelet , chemistry , bone marrow , cellular differentiation , receptor , biology , stem cell , immunology , biochemistry , gene
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 sphin‐gosine 1‐phosphate receptor 4 (S1P 4 ) is specifically up‐regulated during the development of human megakaryo‐cytes 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 eryth‐roleukemia 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., Graler, 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 . FASEB J. 24, 4701–4710 (2010). www.fasebj.org