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

被引：64

作者：

Bender, Markus ^{[1
,2
]}

Eckly, Anita ^{[3
]}

Hartwig, John H. ^{[4
]}

Elvers, Margitta ^{[1
,2
]}

Pleines, Irina ^{[1
,2
]}

Gupta, Shuchi ^{[1
,2
]}

Krohne, Georg ^{[5
]}

Jeanclos, Elisabeth ^{[1
,6
]}

Gohla, Antje ^{[1
,6
]}

Gurniak, Christine ^{[7
]}

Gachet, Christian ^{[3
]}

Witke, Walter ^{[7
]}

Nieswandt, Bernhard ^{[1
,2
]}

机构：

[1] Univ Wurzburg, Deutsch Forsch Gemeinschaft Res Ctr Expt Biomed, Rudolf Virchow Ctr, Wurzburg, Germany

[2] Univ Wurzburg, Univ Hosp, Dept Vasc Med, Wurzburg, Germany

[3] Univ Strasbourg, INSERM, UMR S949, Etab Francais du Sang Alsace, Strasbourg, France

[4] Harvard Univ, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA

[5] Univ Wurzburg, Div Electron Microscopy, Wurzburg, Germany

[6] Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Germany

[7] Univ Bonn, Inst Genet, D-5300 Bonn, Germany

来源：

BLOOD | 2010年 / 116卷 / 10期

关键词：

THROMBOCYTOPENIC PURPURA; PROPLATELET FORMATION; FILAMENT TURNOVER; UNC-60; GENE; N-COFILIN; MEGAKARYOCYTE; PROTEINS; BINDING; ROLES; PHOSPHORYLATION;

D O I：

10.1182/blood-2010-03-274340

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2010; 116(10):1767-1775)

引用

页码：1767 / 1775

页数：9

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