Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
Blood, 15 May 2007, Vol. 109, No. 10, pp. 4229-4236.
Prepublished online as a Blood First Edition Paper on January 23, 2007; DOI 10.1182/blood-2006-04-020024.


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2006-04-020024v1
109/10/4229    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chang, Y.
Right arrow Articles by Debili, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chang, Y.
Right arrow Articles by Debili, N.
Related Collections
Right arrow Hematopoiesis and Stem Cells
Right arrow Hemostasis, Thrombosis, and Vascular Biology
Right arrow Cytoskeleton
Right arrow Signal Transduction
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

HEMATOPOIESIS

Proplatelet formation is regulated by the Rho/ROCK pathway

Yunhua Chang1,2,6, Frédéric Auradé1,2,6, Frédéric Larbret2,6, Yanyan Zhang1,2,6, Jean-Pierre Le Couedic1,2,6, Laurence Momeux3, Jerôme Larghero4, Jacques Bertoglio5, Fawzia Louache1,2,6, Elisabeth Cramer3, William Vainchenker1,2,6, and Najet Debili1,2,6

1 Institut National de la Santé et de la Recherche Médicale (INSERM), Unité (U) 790, Pavillon de Recherche 1, Institut Gustave Roussy, Villejuif, France; 2 Université Paris XI, Institut Fédératif de Recherche (IFR) 54, Institut Gustave Roussy, Villejuif, France; 3 INSERM, U567, Institut Cochin, Département d'Hématologie, Paris, France; 4 Laboratoire de Therapie Cellulaire, Hôpital Saint-Louis, Paris, France; 5 INSERM, U749, Faculté de Pharmacie, Chatenay-Malabry, France; 6 Institut Gustave Roussy, Villejuif, France

Platelets are released by megakaryocytes (MKs) via cytoplasmic extensions called proplatelets, which require profound changes in the microtubule and actin organization. Here, we provide evidence that the Rho/ROCK pathway, a well-known regulator of actin cytoskeleton, acts as a negative regulator of proplatelet formation (PPF). Rho is expressed at a high level during the entire MK differentiation including human CD34+ cells. Thrombopoietin stimulates its activity but at a higher extent in immature than in mature MKs. Overexpression of a dominant-negative or a spontaneously active RhoA leads to an increase or a decrease in PPF indicating that Rho activation inhibits PPF. This inhibitory effect is mediated through the main Rho effector, Rho kinase (ROCK), the inhibition of which also increases PPF. Furthermore, inhibition of Rho or ROCK in MKs leads to a decrease in myosin light chain 2 (MLC2) phosphorylation, which is required for myosin contractility. Interestingly, inhibition of the MLC kinase also decreases MLC2 phosphorylation while increasing PPF. Taken together, our results suggest that MLC2 phosphorylation is regulated by both ROCK and MLC kinase and plays an important role in platelet biogenesis by controlling PPF and fragmentation.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
BloodHome page
S. Kunishima, M. Hamaguchi, and H. Saito
Differential expression of wild-type and mutant NMMHC-IIA polypeptides in blood cells suggests cell-specific regulation mechanisms in MYH9 disorders
Blood, March 15, 2008; 111(6): 3015 - 3023.
[Abstract] [Full Text] [PDF]


Home page
haematolHome page
A. T. Nurden and P. Nurden
Inherited thrombocytopenias
Haematologica, September 1, 2007; 92(9): 1158 - 1164.
[Full Text] [PDF]


Home page
BloodHome page
A. T. Nurden
ROCK and Rho(ll) in bone marrow
Blood, July 1, 2007; 110(1): 5 - 6.
[Full Text] [PDF]


Home page
BloodHome page
Z. Chen, O. Naveiras, A. Balduini, A. Mammoto, M. A. Conti, R. S. Adelstein, D. Ingber, G. Q. Daley, and R. A. Shivdasani
The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway
Blood, July 1, 2007; 110(1): 171 - 179.
[Abstract] [Full Text] [PDF]



 click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020