Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 44, Issue 7, Pages 1121-1132Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2012.03.020
Keywords
CD34; Hematopoietic stem cells; Cell polarity; Migration; Homing
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Funding
- Deutsche Forschungsgemeinschaft [SPP1109 GI 336/1-4]
- Forschungskommission of the HHU-Dusseldorf
- Leukamieliga e.V.
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Freshly isolated human hematopoietic stem and progenitor cells (HSPCs) are small and round cells which upon cultivation adopt a polarized morphology and redistribute certain cell surface antigens. To functionally dissect this polarization process, we addressed impacts of protein synthesis, HSPC trafficking, cytoskeleton organization or lipid raft integrity on the establishment and maintenance of the cell polarity of human HSPCs. Effects on the morphology, sub-cellular distribution of lipid raft-associated molecular polarization markers (Flotillin-1, Flotillin-2, ICAM-3) and in vitro migration capabilities of treated cells were studied. We could distinguish two levels of cellular polarization, a molecular and a morphological level. Our data suggest that protein synthesis, lipid raft integrity and enzymatic activities of PI3K and aPKC are required to organize the molecular cell polarity. The morphological cell polarization process, however, also depends on actin polymerization and rho-GTPase activities. In summary, our data qualify HSPC polarization processes as new pharmaceutical target to interfere with migratory and with homing capabilities of HSPCs. (C) 2012 Elsevier Ltd. All rights reserved.
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