ADF/n-cofilin–dependent actin turnover determines platelet formation and sizing

The cellular and molecular mechanisms orchestrating the complex process by which bone marrow megakaryocytes form and release platelets remain poorly understood. Mature megakaryocytes generate long cytoplasmic extensions, proplatelets, which have the capacity to generate platelets. Although microtubu...

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Bibliographic Details
Published in:Blood 2010-09, Vol.116 (10), p.1767-1775
Main Authors: Bender, Markus, Eckly, Anita, Hartwig, John H., Elvers, Margitta, Pleines, Irina, Gupta, Shuchi, Krohne, Georg, Jeanclos, Elisabeth, Gohla, Antje, Gurniak, Christine, Gachet, Christian, Witke, Walter, Nieswandt, Bernhard
Format: Article
Language:English
Subjects:
Actin Cytoskeleton - drug effects
Actin Cytoskeleton - metabolism
Actins - metabolism
Animals
Biological and medical sciences
Blood Platelets - cytology
Blood Platelets - metabolism
Blood Platelets - ultrastructure
Blotting, Western
Cell Shape
Cell Size
Cell Survival
Cofilin 1 - genetics
Cofilin 1 - metabolism
Cytoskeleton - drug effects
Cytoskeleton - metabolism
Destrin - genetics
Destrin - metabolism
Fibrinogen - metabolism
Hematologic and hematopoietic diseases
Hematology
Human health and pathology
Life Sciences
Medical sciences
Megakaryocytes - cytology
Megakaryocytes - metabolism
Megakaryocytes - ultrastructure
Mice
Mice, Knockout
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Platelet Count
Splenomegaly - genetics
Splenomegaly - metabolism
Splenomegaly - pathology
Thrombin - pharmacology
Time Factors
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Summary:The cellular and molecular mechanisms orchestrating the complex process by which bone marrow megakaryocytes form and release platelets remain poorly understood. Mature megakaryocytes generate long cytoplasmic extensions, proplatelets, which have the capacity to generate platelets. Although microtubules are the main structural component of proplatelets and microtubule sliding is known to drive proplatelet elongation, the role of actin dynamics in the process of platelet formation has remained elusive. Here, we tailored a mouse model lacking all ADF/n-cofilin–mediated actin dynamics in megakaryocytes to specifically elucidate the role of actin filament turnover in platelet formation. We demonstrate, for the first time, that in vivo actin filament turnover plays a critical role in the late stages of platelet formation from megakaryocytes and the proper sizing of platelets in the periphery. Our results provide the genetic proof that platelet production from megakaryocytes strictly requires dynamic changes in the actin cytoskeleton.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2010-03-274340