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DOI | 10.1038/s41467-018-07680-2 |
A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis | |
Duetting, Sebastian1,2,3; Gaits-Iacovoni, Frederique4; Stegner, David1,2; Popp, Michael1,2,3; Antkowiak, Adrien4; van Eeuwijk, Judith M. M.1,2,3; Nurden, Paquita1,2,5; Stritt, Simon1,2,3; Heib, Tobias1,2,3; Aurbach, Katja1,2,3; Angay, Oguzhan3; Cherpokova, Deya1,2,3; Heinz, Niels6,7; Baig, Ayesha A.1,2,3; Gorelashvili, Maximilian G.1,2,3; Gerner, Frank1,2,3; Heinze, Katrin G.3; Ware, Jerry8; Krohne, Georg9; Ruggeri, Zaverio M.10; Nurden, Alan T.5; Schulze, Harald1,2; Modlich, Ute6,7; Pleines, Irina1,2,3; Brakebusch, Cord11; Nieswandt, Bernhard1,2,3 | |
2017-06-15 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Germany; France; USA; Denmark |
英文摘要 | Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation. In the absence of RhoA, increased Cdc42 activity and MK hyperpolarization triggers GPIb-dependent transmigration of entire MKs into BM sinusoids. These findings position Cdc42 (go-signal) and RhoA (stop-signal) at the centre of a molecular checkpoint downstream of GPIb that controls transendothelial platelet biogenesis. Our results may open new avenues for the treatment of platelet production disorders and help to explain the thrombocytopenia in patients with Bernard-Soulier syndrome, a bleeding disorder caused by defects in GPIb-IX-V. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000403317100001 |
WOS关键词 | DEMARCATION MEMBRANE SYSTEM ; PROPLATELET FORMATION ; CELL POLARITY ; MOUSE MODEL ; VASCULAR NICHE ; SMALL GTPASES ; GPIB-ALPHA ; MEGAKARYOCYTE ; MACROTHROMBOCYTOPENIA ; ACTIVATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204118 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Hosp, Inst Expt Biomed, Josef Schneider Str 2, D-97080 Wurzburg, Germany; 2.Univ Wurzburg, Josef Schneider Str 2, D-97080 Wurzburg, Germany; 3.Univ Wurzburg, Rudolf Virchow Ctr, Josef Schneider Str 2, D-97080 Wurzburg, Germany; 4.Univ Toulouse, INSERM, UMR1048, I2MC, 1 Ave Jean Poulhes,BP 84225, F-31432 Toulouse 4, France; 5.Hop Xavier Arnozan, Inst Hosp Univ LIRYC, Plateforme Technol Innovat Biomed, Ave Haut Leveque, F-33604 Pessac, France; 6.LOEWE Ctr Cell & Gene Therapy Frankfurt Main, Res Grp Gene Modificat Stem Cells, Paul Ehrlich Str 51-59, D-63225 Langen, Germany; 7.Paul Ehrlich Inst, Paul Ehrlich Str 51-59, D-63225 Langen, Germany; 8.Univ Arkansas Med Sci, Dept Physiol & Biophys, 4301 West Markham St, Little Rock, AR 72205 USA; 9.Univ Wurzburg, Bioctr, D-97074 Wurzburg, Germany; 10.Scripps Res Inst, Dept Mol Med, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA; 11.Univ Copenhagen, Inst Biomed, BRIC, Norregade 10, DK-1165 Copenhagen, Denmark |
推荐引用方式 GB/T 7714 | Duetting, Sebastian,Gaits-Iacovoni, Frederique,Stegner, David,et al. A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Duetting, Sebastian.,Gaits-Iacovoni, Frederique.,Stegner, David.,Popp, Michael.,Antkowiak, Adrien.,...&Nieswandt, Bernhard.(2017).A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis.NATURE COMMUNICATIONS,8. |
MLA | Duetting, Sebastian,et al."A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis".NATURE COMMUNICATIONS 8(2017). |
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