Microtubule sliding drives proplatelet elongation and is dependent on cytoplasmic dynein

被引：73

作者：

Bender, Markus ^{[1
]}

Thon, Jonathan N. ^{[2
,3
]}

Ehrlicher, Allen J. ^{[4
,5
]}

Wu, Stephen ^{[2
]}

Mazutis, Linas ^{[3
,4
,9
]}

Deschmann, Emoke ^{[6
,7
]}

Sola-Visner, Martha ^{[6
]}

Italiano, Joseph E. ^{[2
,3
,8
]}

Hartwig, John H. ^{[1
]}

机构：

[1] Brigham & Womens Hosp, Dept Med, Div Translat Med, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA

[3] Platelet BioGenesis, Chestnut Hill, MA USA

[4] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA

[5] McGill Univ, Dept Bioengn, Montreal, PQ, Canada

[6] Boston Childrens Hosp, Div Newborn Med, Boston, MA USA

[7] Karolinska Inst, Dept Womens & Childrens Hlth, Div Neonatol, Stockholm, Sweden

[8] Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA USA

[9] Vilnius State Univ, Inst Biotechnol, Vilnius, Lithuania

来源：

BLOOD | 2015年 / 125卷 / 05期

基金：

美国国家卫生研究院;

关键词：

PLATELET PRODUCTION; MARGINAL BAND; MEGAKARYOCYTES; THROMBOPOIESIS; VISUALIZATION; MECHANISMS; INHIBITORS; RELEASE; INVITRO; CELLS;

D O I：

10.1182/blood-2014-09-600858

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Bone marrow megakaryocytes produce platelets by extending long cytoplasmic protrusions, designated proplatelets, into sinusoidal blood vessels. Although microtubules are known to regulate platelet production, the underlying mechanism of proplatelet elongation has yet to be resolved. Here we report that proplatelet formation is a process that can be divided into repetitive phases (extension, pause, and retraction), as revealed by differential interference contrast and fluorescence loss after photoconversion time-lapse microscopy. Furthermore, we show that microtubule sliding drives proplatelet elongation and is dependent on cytoplasmic dynein under static and physiological shear stress by using fluorescence recovery after photo bleaching in proplatelets with fluorescence-tagged beta 1-tubulin. A refined understanding of the specific mechanisms regulating platelet production will yield strategies to treat patients with thrombocythemia or thrombocytopenia.

引用

页码：860 / 868

页数：9

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